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Noticias de la lucha contra el cáncer

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Lung cancer pill cuts risk of death by half, says ‘thrilling’ study
Andrew Gregory, Health editor in Chicago, Sun 4 Jun 2023 13.00 BST

Taking the drug osimertinib once a day after surgery reduces chance of patients dying by 51%, trials show

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The survival benefit of osimertinib ‘was observed consistently’ in an analysis across all study subgroups, the study says. Photograph: utah778/Getty Images/iStockphoto

A pill taken once a day cuts the risk of dying from lung cancer by half, according to “thrilling” and “unprecedented” results from a decade-long global study.

Taking the drug osimertinib after surgery dramatically reduced the risk of patients dying by 51%, results presented at the world’s largest cancer conference showed.

Lung cancer is the world’s leading cause of cancer death, accounting for about 1.8 million deaths a year. The results of the late-stage study, led by Yale University, were presented at the American Society of Clinical Oncology’s (Asco) annual meeting in Chicago.

“Thirty years ago, there was nothing we could do for these patients,” said Dr Roy Herbst, the deputy director of Yale Cancer Center and lead author of the study. “Now we have this potent drug."

“Fifty per cent is a big deal in any disease, but certainly in a disease like lung cancer, which has typically been very resistant to therapies.”

The Adaura trial involved patients aged between 30 and 86 in 26 countries and looked at whether the pill could help non-small cell lung cancer patients, the most common form of the disease.

Everyone in the trial had a mutation of the EGFR gene, which is found in about a quarter of global lung cancer cases, and accounts for as many as 40% of cases in Asia. An EGFR mutation is more common in women than men, and in people who have never smoked or have been light smokers.

Speaking in Chicago, Herbst said the “thrilling” results added huge weight to earlier findings from the same trial that showed the pill also halves the risk of a recurrence of the disease.

Herbst, the assistant dean for translational research at Yale School of Medicine, said the pill was proven to be “practice-changing” and should become the “standard of care” for the quarter of lung cancer patients worldwide with the EGFR mutation.

Some patients in the UK, US and other countries are already able to access the drug, he said, but more should benefit.

Not everyone diagnosed with lung cancer is tested for the EGFR mutation, which needs to change, Herbst said, given the study’s findings. “This further reinforces the need to identify these patients with available biomarkers at the time of diagnosis and before treatment begins.”

Treatment after surgery with osimertinib, also known as Tagrisso and made by AstraZeneca, “significantly lowered” the risk of death in lung cancer patients, the trial results reported. “Adjuvant osimertinib demonstrated an unprecedented, highly statistically significant and clinically meaningful overall survival benefit in patients,” the report said.

After five years, 88% of patients who took the daily pill after the removal of their tumour were still alive, compared with 78% of patients treated with a placebo. Overall, there was a 51% lower risk of death for those who received osimertinib compared with those who received placebo.

The survival benefit “was observed consistently” in an analysis across all study subgroups, including those with stage one, stage two and stage three lung cancer. Chemotherapy had been given to 60% of those in the study, and the survival benefit of osimertinib was seen regardless of whether prior chemotherapy was received.

“It is hard to convey how important this finding is and how long it’s taken to get here,” said Dr Nathan Pennell, an Asco expert who was not involved with the study. “This shows an unequivocal, highly significant improvement in survival.”

Angela Terry, the chair of EGFR Positive UK, a lung cancer charity, said the findings were “very exciting” and “hugely significant”.

“A five-year overall survival rate of 88% is incredibly positive news,” she said. “Having access to a drug whose efficacy is proven and whose side-effects are tolerable means patients can be confident of and able to enjoy a good quality of life for longer.”

https://www.theguardian.com/science/202 ... ling-study
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Combo therapy trial achieves 94% remission rate for Hodgkin's lymphoma
Michael Irving, June 13, 2023

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A new clinical trial has shown promise in treating Hodgkin Lymphoma, which affects the lymph nodesDepositphotos

A combination of chemotherapy and immunotherapy has proven promising in treating patients with advanced Hodgkin Lymphoma, and removes the need for radiation therapy in kids. In a new phase 3 clinical trial, 94% of patients receiving the combo treatment were in remission after one year.

Hodgkin Lymphoma is a relatively rare kind of cancer that affects the lymph nodes. It mostly strikes younger people, between the ages of 20 and 40, and can often be treated with chemotherapy or radiation therapy.

A new clinical trial has now investigated adding immunotherapy to the mix. It ran between July 2019 and October 2022 and involved almost 1,000 patients with stage 3 or 4 Hodgkin Lymphoma. The trial compared a standard treatment of chemotherapy with the drug brentuximab vedotin, against a pairing of chemotherapy and an immunotherapy drug called nivolumab.

And sure enough, the group that received the immunotherapy and chemotherapy combo saw 94% of patients entering remission, with follow-up over the course of a year. Out of hundreds of people, there were only four deaths in that group, compared to 11 in the group receiving chemotherapy alone, which saw 86% of patients achieve remission.

In fact, the team says that the trial was so successful the National Cancer Institute (NCI) ordered it be halted early so that the FDA could expedite approval of the therapy to treat stage 3 and 4 Hodgkin Lymphoma.

“The results are remarkable,” said Alex Herrera, lead investigator of the trial. “The combination of nivolumab and chemotherapy is potent and safe in patients with stage 3 or 4 classic Hodgkin lymphoma as an initial treatment. This is indeed great news for patients with this cancer, as there is another effective and safe option for them.”

Importantly, a key part of the trial was the inclusion of patients as young as 12. Radiation therapy is a common treatment for this group, but not only is that more unpleasant in the moment but it carries a higher risk of serious side effects later in life. In this study, it was effectively replaced by immunotherapy.

“By eliminating radiation for children enrolled in this trial, we essentially took away the risks of many toxic late effects,” said Jonathan Friedberg, senior investigator of the study. “But we only have one year of follow-up data for our trial at this point, and we will continue to watch for side effects in the future.”

Source: University of Rochester Medical Center

https://newatlas.com/medical/hodgkins-l ... remission/
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Nuevo análisis de sangre podría ayudar a detectar el cáncer
Anna Carthaus, Deutsche Welle, 13-Jun-2023

Un análisis de sangre resulta prometedor para detectar más de 50 tipos de cáncer en pacientes con síntomas.

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La sangre puede dar indicios de cáncer. Imagen: Waltraud Grubitzsch/dpa-Zentralbild/picture alliance

Cuando recibió el diagnóstico, ya era demasiado tarde. El cáncer había consumido el páncreas y se había extendido a los órganos vecinos. La cirugía ya no era una opción. Cuatro meses después, a la edad de 31 años, el joven, natural de Alemania, había muerto.

Aunque el tratamiento del cáncer ha mejorado en los últimos años, a menudo fracasa porque los tumores se detectan demasiado tarde. Especialmente en una fase temprana, síntomas como el dolor de estómago o la fatiga suelen ser difusos, lo que hace que los pacientes acudan al médico sólo cuando la enfermedad ya es difícil o imposible de tratar. Pero un análisis de sangre llamado Galleri pretende cambiar esta situación.

Los desarrolladores de la empresa sanitaria estadounidense Grail afirman que este análisis es capaz de detectar más de 50 tipos de cáncer en una simple muestra de sangre. A principios de este mes, los científicos presentaron los resultados del estudio en la mayor conferencia mundial sobre el cáncer, la reunión anual de la Sociedad Estadounidense de Oncología Clínica (ASCO, por sus siglas en inglés).

El análisis de sangre, fiable dos de cada tres veces
El equipo que llevó a cabo la investigación, dirigido por científicos de la Universidad de Oxford, empleó este examen en un total de 5.400 pacientes que presentaban síntomas indicativos de cáncer. Antes de someterse a una prueba estándar, los pacientes cedieron una muestra de sangre para su análisis a través del exámen Galleri. En dos de cada tres pacientes a los que finalmente se diagnosticó cáncer mediante el procedimiento estándar, hubo indicios de la enfermedad en el análisis de sangre.

No obstante, en 79 participantes el análisis dio falsos positivos. Algo "problemático", explica a DW Mark Middleton, investigador principal del estudio.

Facilitar pruebas más rápidas y terapia temprana como potencial
Muchos investigadores y médicos están encantados con que un análisis de sangre pueda ayudar a la detección precoz del cáncer, ya que las tasas de supervivencia podrían ser mucho más altas.

Otra ventaja de la prueba Galleri es que encuentra más de 50 tipos diferentes de cáncer, incluidos los que suelen detectarse de forma muy tardía y con bajas tasas de supervivencia, como el de ovario o el de páncreas, o de los que no existe un cribado rutinario.

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Ilustración en 3D de células cancerosas.Imagen: ersin arslan/Zoonar/picture alliance

Detección de fragmentos de ADN tumoral en la sangre
Cuando una célula muere, su ADN pasa al torrente sanguíneo. El ADN de las células cancerosas se diferencia del de las células sanas en que tiene indicadores específicos, en concreto, un patrón específico de metilación. La prueba Galleri es capaz de detectar este patrón.

El patrón difiere de un tipo de célula a otro, por lo que el análisis también puede detectar de qué parte del cuerpo proceden las células cancerosas.

"Eso puede ser enormemente útil para asegurarse de que se hacen las pruebas adecuadas", afirma Middleton.

A tener en cuenta
Por el momento, el punto fuerte del análisis es que desencadena nuevas pruebas. "Un resultado positivo no es un diagnóstico de cáncer. Lo que dice es: haz más pruebas para encontrarlo", señaló Middleton.

De momento hay un factor limitante: la prueba depende de la presencia de cierta cantidad de material genético en el torrente sanguíneo. Si una célula tumoral no produce suficiente material genético, el análisis no puede detectarla.

(aa/ers)

https://www.dw.com/es/nuevo-an%C3%A1lis ... a-65895241
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Aberdeen AI trial helps doctors spot breast cancers
By Marc Cieslak & Liv McMahon, BBC, 09/07/2023

A trial under way at Aberdeen Royal Infirmary is exploring whether artificial intelligence (AI) can assist radiologists in reviewing thousands of mammograms a year.

The pilot helped spot early-stage breast cancer for June - a healthcare assistant and participant in the trial - and she is now set to undergo surgery as a result.

Mammograms are low level X-rays used in breast cancer screenings to monitor and detect changes too small to see or feel.

According to the NHS, they help save about 1,300 lives each year in the UK.

And while the number of women who attended a routine breast screening, after an invitation, increased in Scotland in the three-year period to 2022, the number of radiologists to review results is shrinking.

What is AI?
AI - technology which sees computers perform specific tasks that would typically require human intelligence - is already widely used across a range of industries.

While high-profile experts' fears that AI could lead to the extinction of humanity have recently been making headlines, the tech's more practical realities are already being shown in healthcare.

Its potential to speed up the process of drug and disease discovery means many scientists and doctors see AI as a powerful tool to work with, rather than replace, practitioners.

Aberdeen's AI trial

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AI radiology in breast cancer screenings is being trialled at Aberdeen Royal Infirmary

The number of screen-detected breast cancers of women of all ages grew to 1,830 between 2021 and 2022 in Scotland, according to Public Health Scotland (PHS) data.

Of the 5,000 mammograms scrutinised on average by radiologists each year, between 250 and 300 patients will be called back - with 30 to 40 of them requiring closer attention.

"There is a chance that with that number, you could miss cancers," Dr Gerald Lip, clinical director of the North East Scotland Breast Screening Programme, told BBC Click.

NHS Grampian's Gemini project - a collaboration between the NHS, the University of Aberdeen and private industry - was mentioned in Scotland's AI Strategy when it launched in 2021.

Kheiron Medical Technologies developed the AI model Mia, used in the trial, with Microsoft providing the cloud computing services to support it.

With rules set by the National Screening Counsel currently forbidding the automatic deployment of AI in screenings, Dr Lip and other radiologists are trialling it as an additional check at the end of mammogram scan reviews.

June, a participant in the trial who has undergone similar surgery before, received a biopsy to remove a small part of her breast tissue for testing after Dr Lip explained how the AI tool helped identify an area of concern.

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Dr Lip talks June through the changes the AI software detected in her mammogram

He showed BBC Click how the software works using anonymised mammogram results.

"What we're seeing now is a lady who's got mammograms on the left side and right side, you're looking for differences," he said.

By clicking a button, radiologists can view and check differences identified by the AI between the two scans.

Dr Lip pointed to one area circled by the AI software, identifying it as the main area of concern.

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Areas of concern circled on a mammogram by AI software

"In screening you want to pick up things when they are small before they become big," he added.

A few weeks after her biopsy, June told Click that using AI - rather than another human pair of eyes - made the process feel less intrusive.

"You know your images are on screen, and people are looking at them," she said. "Whereas when it's an artificial intelligence, that bit of feeling that somebody is looking has gone."

The results of June's biopsy means she will once again be having surgery.

"The biopsy showed that I do have an early-stage cancer, they've certainly caught it at an earlier stage this time," June said. "But because I've had previous history with it, I'm going to go in and have a mastectomy.

"It's not treatment I want to have. But at the same time, it's reassuring that it's being caught."

'Chronic staff shortages'
A major review of Scotland's breast screening programme published last year suggested a large number of radiology and advance practitioner staff are either nearing or at retirement age.

It said the decline of "super reader" radiologists, relied on by the service to review a particularly high number of results, risks leaving the service "vulnerable".

The Royal College of Radiologists has also warned the UK is facing "chronic staff shortages", with patients waiting too long for vital tests and cancer treatments.

A radiologist reviews mammograms at Aberdeen Royal Infirmary
With two radiologists needed to read and report results, the Scottish government's review said replacing one human reader with AI could "cover half of the screening image reading burden of approximately 1.72 million images read each year".

But could the technology being tested in Aberdeen some day replace human staff?

"I think the goal of this evaluation is to see what's the best way we can work with AI, whether it's replacing one of the radiologists, whether it's part reading some of the normal mammograms, or whether it's to improve our cancer detection as a safety net," Dr Lip said.

Peter Kecskemethy, co-founder of Kheiron, said the tech will used by more than 30 NHS trusts across the UK for millions to access.

And with trusts in England already exploring how AI can support better, faster outcomes for breast cancer patients, the tech looks to continue playing a large role in helping doctors save lives.

https://www.bbc.com/news/technology-65821552
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The therapy uses souped-up immune cells to fight multiple myeloma.
B. David Zarley, June 12, 2023

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Credit: National Cancer Institute

Anew cancer therapy developed at Jerusalem’s Hadassah-University Medical Center had a 90% response rate in a new clinical trial, with over half of patients going into total remission. The CAR-T therapy — which arms the body’s own immune cells to fight cancer — was able to send multiple myeloma, an extremely deadly cancer that impacts the immune system, into remission.

The therapy is the result of years worth of experiments conducted by the hospital’s bone-marrow transplant and immunotherapy department, the Jerusalem Post reported.

“We have evidence of a very positive overall response rate with minimal side effects, and they are mild,” Polina Stepensky, the head of the bone marrow transplantation and cancer immunotherapy department, told the Jerusalem Post.

“These are dramatic results. This is a huge hope for patients with a disease that has not yet had a cure.”

A new CAR-T therapy for multiple myeloma had a 90% response rate in a clinical trial.

What is multiple myeloma? Multiple myeloma is a rare but deadly blood cancer, stemming from a kind of white blood cell called plasma cells. Normally, these cells reside in the bone marrow, cranking out antibodies to help fight infection. But cancerous plasma cells are a serious threat.

The malignant cells begin producing abnormal antibodies that do not fight infection, while also elbowing out blood-forming cells in the marrow, impacting your ability to create enough healthy red blood cells and platelets (the little fellas charged with forming clots to staunch or slow bleeding).

This blood cancer causes anemia; bone pain and fracture risk; kidney problems (stemming from those junk antibodies clogging up the organ’s filters); blood thickening, making it harder to pump blood effectively; and susceptibility to infection.

According to government estimates, about 35,000 people will develop myeloma in the US this year and about 12,500 will die from it.

Starting the CAR: Stepensky was inspired to work on a CAR-T therapy for multiple myeloma after seeing the treatment in action at New York’s Memorial Sloan Kettering Cancer Center in 2017, Hadassah Magazine reported.

“When I graduated from Hadassah Medical School in 1998, median survival for multiple myeloma patients was less than three years,” Stepensky told the magazine. “With new medications and bone marrow transplantation, we’ve stretched this to over a decade. But in the end, all existing therapies lose effectiveness. We needed another approach.”

“These are dramatic results. This is a huge hope for patients with a disease that has not yet had a cure.”

POLINA STEPENSKY
CAR-T seemed to be that approach. In CAR-T therapy, the patient’s T cells — a different kind of white blood cell — are extracted and given “chimeric antigen receptors,” or CARs. The CAR allows the T cell to spot the cancerous cells and go on the attack.

Stepensky teamed up with Bar-Ilan University immunologist Cyrille J. Cohen to develop a specific CAR protein target to fight multiple myeloma.

“It took many different designs until we identified the optimum molecule, but we got there,” Cohen told Hadassah Magazine.

The trial: In their newest trial, 74 multiple myeloma patients received the CAR-T therapy. Over half of the patients went into complete remission, Israel21C reported, with 90% responding to the therapy.

There are now over 200 patients from across the globe on waiting lists for the therapy, which is still only conducted as a trial. Because of the therapy’s complexity, only one patient can enter treatment per week, Stepansky said.

US-based IMMX Bio has a patent license for the therapy, with a US trial slated to start soon, Stepansky said. The hope is to have the treatment approved by the FDA within a year.

https://www.freethink.com/health/multiple-myeloma-car-t
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mRNA Trojan Horse tricks cancer into making toxins to kill itself
Michael Irving, July 04, 2023

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Lipid nanoparticles carry mRNA sequences to cancer cells, causing them to produce toxins that kill the tumors Depositphotos

Scientists have developed and tested a new potential treatment for cancer that works in a similar way to the COVID-19 vaccines. The technique involves delivering mRNA molecules to cancer cells and tricking them into producing toxic proteins that kill the tumors.

Inside all living cells are ribosomes, which are essentially tiny factories that produce proteins. Exactly which proteins they make depends on the 'blueprints' they receive, and these come from messenger RNA (mRNA) molecules.

Over the past few decades, scientists have found that they can hijack this mechanism to make beneficial proteins on demand. This mRNA technology was greatly accelerated by the COVID-19 pandemic, as BioNTech and Moderna developed vaccines that worked by coaxing our cells to produce spike proteins similar to the virus, triggering an immune response that trained our body to fight off subsequent infections.

Since then, scientists have turned their sights onto cancer, experimenting with using mRNA to produce proteins that mimic those made by tumors, helping to launch an immune response against the cancer. This could be particularly promising when paired with other treatments like immunotherapy.

But for the new study, scientists at Tel Aviv University in Israel created an mRNA cancer treatment that works in a different way. The mRNA molecules are encoded to produce a toxin that bacteria make, and are then packaged into lipid nanoparticles and injected into the tumors. This causes the cells to start producing the toxin, and effectively poison themselves. The team says this could be a safer option than chemotherapy, which also harms healthy cells.

“With a simple injection to the tumor bed, we can cause cancer cells to 'commit suicide,' without damaging healthy cells,” said Professor Dan Peer, co-lead author of the study. “Moreover, cancer cells cannot develop resistance to our technology as often happens with chemotherapy – because we can always use a different natural toxin.”

In tests in mice with melanoma, between 44 and 60% of the cancer cells were destroyed after a single injection. The tumor growth slowed and the mice showed significantly improved survival rates over control mice. No adverse effects were seen in the animals.

As intriguing as the idea sounds, it’s important to keep in mind that it’s very early days for the research. There’s no guarantee that results will carry across to humans, and more large-scale animal testing will need to be done first.

The research was published in the journal Theranostics.

Source: Tel Aviv University

https://newatlas.com/medical/mrna-troja ... er-toxins/
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Novel compound stalls the spread of breast cancer
Paul McClure, July 24, 2023

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Researchers have developed a compound that inhibits a protein that causes breast cancer to spread throughout the body Depositphotos

Most people with breast and other cancers die not from the primary tumor but from metastasis, when the cancer spreads throughout the body. Researchers have developed a compound that blocks the actions of a metastasis-causing protein, potentially reducing the spread of breast cancer.

Metastatic breast cancer – also called metastases, secondary tumors or secondaries – occurs when cancer cells break away from the original tumor and travel through the blood or lymphatic system to another part of the body, commonly the bones, lungs, brain, or liver.

Some cancers are more likely to metastasize than others, with research suggesting that specific genes or proteins are involved in the process. One such protein, S100A4, is expressed in metastatic cancers and has been associated with the premature death of people with cancers of the breast, bladder, pancreas, prostate, esophagus, lung and stomach. Rather than directly causing tumor growth, S100A4 has been shown to activate metastasis pathways in the body.

Now, a new study by researchers at the University of Liverpool, UK, and Nanjing Medical School in China looked closely at S100A4 and may have discovered a way to block its production, reducing the likelihood that the cancer will spread.

“As a general rule, cancer that has spread is treated with chemotherapy, but this treatment can rarely be given without severely harming or becoming toxic to the patient,” said Philip Rudland, one of the study’s corresponding authors. “The [importance] of our work was to identify a specific and important target to attack, without toxic side effects.”

The researchers used rat and human model systems of cells from the highly metastatic and incurable type of breast cancer that doesn’t have any of the three commonly found receptors for the hormones estrogen and progesterone and the protein human epidermal growth factor 2 (HER2). Known as triple-negative breast cancer (TNBC), it accounts for 10% to 15% of all breast cancers.

The next step was to identify a compound that inhibited the binding of protein S100A4 with calcium and prevented the metastatic pathway from commencing. A library of 2,400 compounds from Cancer Research UK was screened, and one compound, CT070909, was found to inhibit over 90% of S100A4 binding. Because CT070909’s molecular composition made it relatively insoluble, the researchers synthesized a structurally simpler compound, US-10113.

Testing US-10113 on the model systems, the researchers found it was “moderately weak” at inhibiting S100A4 binding. To improve the efficiency of US-10113, the researchers chemically coupled it to thalidomide, a type of targeted cancer drug used to treat myeloma, a type of blood cancer. Thalidomide stops cancer cells from dividing and growing, stops cancers from creating the blood supply they need to be able to grow, and stimulates some of the immune system cells to attack cancer cells.

They found that the combined thalidomide-US-10113 compound specifically eliminated S100A4 in rat and human TNBC cells, with a nearly 20,000-fold increase in efficiency compared to US-10113 alone. They saw few signs of toxicity.

“This is an exciting breakthrough in our research,” said Gemma Nixon, another of the study’s corresponding authors. “We now hope to take the next steps and repeat this study in a large group of animals with similar metastatic cancers so that the efficacy and stability of the compounds can be thoroughly investigated and, if necessary, improved by further design and syntheses, prior to any clinical trials.”

The researchers say their findings demonstrate proof-of-principle of a chemotherapeutic approach to selectively inhibit cancer metastases. Moreover, because the protein S100A4 is present in different kinds of cancers, it may lead to the development of a treatment for more than breast cancer.

“Significantly, this particular protein we’re investigating occurs in many different cancers, which could mean this approach may be valid for many other commonly occurring human cancers.”

The study was published in the journal Biomolecules.
Source: University of Liverpool

https://newatlas.com/medical/novel-comp ... er-spread/
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New discovery could prove pivotal in stopping cancer spreading
Bronwyn Thompson, July 24, 2023

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More than 90% of cancer deaths are the result of the disease metastasizing Deposit photos

In a discovery that took researchers by surprise, a protein known to play a crucial role in cancer growth has for the first time been observed traveling into cell nuclei to flick switches that make cancers more mobile, aggressive and invasive.

Suppressing this mechanism could potentially help contain a variety of cancers such as lung, kidney, stomach and prostate, making targeted treatment more effective. More than 90% of cancer deaths are the result of the spread of cells to other parts of the body, or metastasis.

Stress is well understood to be a factor in cancer metastasizing. Now, scientists have found that when cancer cells are feeling the pressure, the chaperone protein GRP78 (also often referred to as BIP), which resides in the endoplasmic reticulum (ER), migrates to the nucleus to ‘hijack’ gene activity. This essentially reprograms cell behavior, making cancers more difficult to contain.

“Seeing GRP78 in the nucleus controlling gene expression is a total surprise,” said senior author Amy S. Lee, professor of biochemistry and molecular medicine at the Keck School of Medicine of USC. “When it comes to the basic mechanisms of cancer cells, this is something novel that, to my knowledge, no-one has observed before.”

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In the bottom row, cells lacked GRP78 in the nucleus. The green staining depicts the cytoskeletal protein F-actin which controls cell shape and motility and the blue staining depicts the nucleus - Ze Liu, Amy Lee/Keck School of Medicine of USC

Earlier studies have pinpointed the important role GRP78 plays in cancer cell survival and proliferation, but the ways in which it facilitates this have not been fully understood. The protein has also been implicated in the replication of the COVID-19 virus, increasing the likelihood of mutations that lead to different and more vaccine-resistant strains.

Chaperone proteins aid the folding of other proteins inside the cell, and GRP78 has been thought to only exist in the ER. Through complex RNA sequencing, the scientists were able to see how, under stress, it moved into the ‘brain’ of the cell to regulate the gene EGFR and bind to protein inhibitor ID2.

This ‘hostile takeover’ leads to ID2 being unable to lock down gene expression of EGFR, resulting in an upswing of its activity, which makes cancer cells more mobile and invasive.

“To our big surprise, we found that the key genes being regulated by GRP78 in the nucleus are mainly involved with cell migration and invasion,” Lee said.

Treatments to stop GPR78 in its tracks, or prevent it binding to ID2, presents a new avenue of research and development for scientists. While this study looked at lung cancer cells, GPR78 functions similarly in many other cancers. And there may be other proteins that assume different roles that alter cell behavior when they’re triggered and migrate.

“This is a new concept,” Lee said. “The protein itself is the soldier that does the job, but now we’re thinking it’s not just about the soldier, but also where the solider is deployed.”

The team is now looking at therapies to block the chaperone protein expression, including known ER stress inducer and GRP78 inhibitor YUM70.

The research was published in journal Proceedings of the National Academy of Sciences.
Source: Keck School of Medicine of USC

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Replacing a critical nutrient with a mimic starves pancreatic cancer
Paul McClure, October 09, 2023

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Researchers have found a way to starve pancreatic cancer cells, slowing their growth and spreadScientific Animations Inc/Wikimedia Commons (CC BY-SA 4.0)

Researchers have found that replacing a nutrient that pancreatic cancer cells rely on to survive and grow with a copycat version starves the cancer, slowing its spread. The finding opens the door to an entirely new approach to treating this deadly type of cancer.

Pancreatic cancer has one of the lowest survival rates of all cancers. Even if the cancer is caught before it becomes too advanced or spreads, the average survival time is only three to three-and-a-half years. One of the challenges of treating pancreatic cancer has to do with the properties of the tumors themselves.

In a new study, researchers at Stanford Burnham Prebys Medical Discovery Institute, California, exploited the unique properties of pancreatic tumors and used them to halt the cancer’s growth and spread.

“Pancreatic tumors tend to be packed in dense connective tissue that keeps them encapsulated from the rest of the body and cuts off their supply of oxygen,” said Cosimo Commisso, corresponding author of the study. “As a consequence, these cancers develop unique metabolic properties compared to other tumors, and this is something we may be able to exploit with new treatments.”

One thing that sets pancreatic cancer apart from other cancers is its reliance on the nutrient glutamine, which its cells use to survive and proliferate. So, in mice the researchers used 6-Diazo-5-oxo-L-norleucine (DON), which is structurally similar to glutamine but can’t be used as a fuel source, and found that it significantly slowed tumor growth and stopped its spread.

Aware that pancreatic cancer cells can use other nutrients when glutamine’s not available, the researchers combined DON with an existing cancer treatment to block the cells’ access to another important nutrient, asparagine.

“With DON, the cancer cells can’t use glutamine, but they can start to depend on other nutrients as a backup, including asparagine,” Commisso said. “We thought that if we could stop them from using glutamine and asparagine, the tumors would run out of options.”

Cells need asparagine to make proteins and create new cells, and L-asparaginase is a chemotherapy drug that breaks down asparagine, inhibiting cell division and growth. The researchers observed that combining DON and L-asparaginase produced a synergistic effect, helping prevent the spread of pancreatic tumors to other organs.

While DON has been through early clinical trials as a lung cancer treatment, and L-asparaginase is already being used, this is the first time the two have been used together.

“This is particularly exciting because exploring it further for pancreatic cancer patients could be relatively simple since the study designs exist for other solid tumors,” said Commisso. “This could be a game changer for pancreatic cancer, and a lot of the preclinical work needed to rationalize it is already happening.”

The study was published in the journal Nature Cancer. (NB! por subscripción)

Source: Stanford Burnham Prebys

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Once-a-day pill for stubborn cancer delivers a 62.5% positive response
Bronwyn Thompson, December 05, 2023

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An illustration of the KRAS-G12C protein inside a cancer cell, and how divarasib can target it-Peter MacCallum Cancer Centre

In what has already been tagged as a “game-changer” for cancer treatment, the potent once-a-day tablet known as divarasib has continued to impress at Phase 1b trial stage, outperforming not just current therapies but its previous trial results.

Following on from a standalone clinical trial earlier this year, divarasib has now been combined with the existing targeted therapy drug cetuximab, and has delivered a 62.5% positive outcome for people with advanced or metastatic colorectal cancer (CRC) linked to the KRAS G12C gene mutation.

In the first trial, at the Peter MacCallum Cancer Center in Australia, CRC patients receiving just divarasib had a 35.9% positive response rate, which was considered extremely promising.

KRAS is a key protein that regulates how cancer cells behave. For cancer patients with the KRAS G12C gene mutation, their cancer cells are far more likely to divide uncontrollably and form tumors, making the disease very challenging to treat with existing medication. As such, even though it affects around 4% of CRC patients, it has a poor prognosis.

The latest research, again led by Professor Jayesh Desai at the Peter MacCallum Cancer Center, indicates that when taken in conjunction with cetuximab, divarasib targets this mutation and is effective at slowing the development of tumors, while also being well tolerated with few adverse effects.

“The median progression-free survival for patients in the study was just over eight months and the treatment was well tolerated with manageable side effects,” Desai said. “While this is not a head-to-head trial, the response rates are better than what we have seen with other treatments that work on the KRAS G12C mutation pathway.

“We are very hopeful that this combination of divarasib with cetuximab will translate into better outcomes for our colorectal cancer patients,” he added.

While the KRAS G12C mutation is perhaps most associated with CRC, it plays a key role in the expedited progress of other cancers, such as non-small cell lung cancer (detected in around 13% of patients).

Current treatment for KRAS G12C-positive CRC patients includes 5-FU-based chemotherapy with irinotecan, oxaliplatin and/or capecitabine, however, it faces limitations due to low targeting of specific tumors and toxicity.

Earlier this year, the cancer center began a global Phase I trial of divarasib treatment on 137 cancer patients. Research found that the drug was 50 times more specific and 20 times more potent than other similar agents that are currently being used to treat the KRAS mutation.

“It has taken us years of research to build a more thorough understanding of how to target the KRAS mutation and to refine the science so we can develop molecules that are more even more potent,” Desai said in August. “This once daily tablet treatment is true precision medicine specifically targeting the genetic mutation that is driving the cancer.”

The research was published in the journal Nature Medicine.

Source: Peter MacCallum Cancer Centre via Scimex

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Cómo funciona el nuevo análisis de sangre que detecta 18 tipos de cáncer en etapas tempranas
Ashkan Afshin, 15/01/2024
Investigadores desarrollaron un test de proteínas plasmáticas que mejora la detección temprana de diferentes clases de tumores. Los detalles del estudio publicado en BMJ Oncology

La detección temprana del cáncer puede mejorar significativamente los resultados de los pacientes. Los esfuerzos recientes para lograr esto se han centrado principalmente en técnicas de imagen y enfoques de biopsia líquida, como las pruebas de ADN de tumores circulantes. La proteómica, el estudio a gran escala de las proteínas, representa una vía potencial para la detección temprana del cáncer.

Sin embargo, el uso de proteínas plasmáticas como biomarcadores para la detección temprana del cáncer ha sido un desafío debido a la complejidad del proteoma y la falta de sensibilidad en la detección de proteínas de baja abundancia.

Un estudio publicado recientemente confirmó que gracias al desarrollo de un nuevo test, la medición de las proteínas plasmáticas en la sangre mediante una prueba de detección del proteoma puede detectar 18 tipos diferentes de cánceres en sus primeras etapas de desarrollo, en comparación con otros enfoques.

Según datos de la nueva evidencia publicada en la prestigiosa revista científica BMJ Oncology, se desarrolló una nueva prueba de detección de múltiples cánceres en sangre para dar con la enfermedad en etapa temprana con alta precisión, intentando saltar la barrera en las pruebas de detección precoz para muchos tipos de cánceres que, hasta ahora, no estaban disponibles.

En la actualidad, el cáncer es una de las principales causas de muerte en todo el mundo y representa una de cada seis defunciones, según un estudio anterior del mismo equipo de trabajo del Novena de Palo Alto en California, EEUU. Se trata de un laboratorio especializado en la investigación de detección temprana de diferentes dolencias.

Casi el 60 % de los fallecimientos relacionados con el cáncer se deben a tumores para los cuales no existen pruebas de detección disponibles. Además, los métodos comúnmente utilizados, como las colonoscopias, las tomografías computarizadas y las mamografías, entre otros, tienen desventajas, como la invasividad, los altos costos y la precisión limitada en la detección de las primeras etapas.

Enfoques como la biopsia líquida, que analiza biomarcadores en muestras no sólidas, son prometedores, pero las pruebas multicáncer basadas en la genómica muestran una baja sensibilidad para las primeras etapas y pueden ser costosas. En el trabajo publicado en BMJ, se advierte que los biomarcadores de proteínas actuales en la sangre carecen de distinción y sensibilidad para la detección del cáncer.

En este nuevo método, los especialistas exploraron las proteínas plasmáticas como biomarcadores de tumores sólidos, centrándose en la necesidad de detectar marcadores de proteoma indetectables. Para ello, se recolectaron muestras de plasma de 440 pacientes a quienes se les diagnosticó 18 tipos distintos de cáncer con tumores sólidos en etapa temprana o que estaban completamente sanos.

Mediante el uso de ensayos de extensión de proximidad, se midieron más de 3.000 proteínas de alta y baja abundancia en cada muestra, identificando con éxito el sitio de origen del cáncer en más del 80 % de los casos. Siendo que se utilizó un enfoque estadístico de varios pasos, y se identificaron un conjunto limitado de proteínas específicas de cada sexo que podrían detectar cánceres en etapa temprana y su tejido de origen con alta precisión.

Los paneles de detección de cáncer específicos por sexo se elaboraron con 10 proteínas que tenían una alta precisión para hombres y mujeres. En la etapa I, con una distinción del 99 %, estos paneles detectaron el 93 % de los cánceres en hombres y el 84 % en mujeres. La prueba de proteínas plasmáticas reveló que ellas pertenecían principalmente al segmento de baja concentración del proteoma del plasma humano.

En general, los resultados de la prueba de plasma basada en proteínas han mostrado una alta sensibilidad en la detección de una variedad de tumores en etapa temprana en pacientes con cáncer, lo que la convierte en un fuerte candidato para su uso como herramienta de detección. La prueba destaca por su alta distinción, asequibilidad y eficacia, lo que permite reducir la muerte y la enfermedad.

Algunas limitaciones del estudio incluyeron el tamaño de cohorte relativamente pequeño, lo que puede afectar la generalización de su población. Además, ante la posible falta de datos sobre enfermedades y su enfoque exclusivo en los cánceres en etapa temprana, es posible que no representen completamente a las diversas poblaciones de pacientes o en etapas avanzadas.

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Más una nota de prensa que una noticia (la fuente es el productor) pero de interés en todo caso.

AI-powered device to detect all 3 common skin cancers okayed for doctors
Paul McClure, 25/01/2024

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The FDA has granted clearance to an AI-powered device that helps physicians detect skin cancers DermaSensor

The FDA has granted clearance for the first AI-powered handheld medical device to assist physicians in detecting all three common skin cancers: basal cell carcinoma, squamous cell carcinoma, and melanoma. Providing a more accurate way of identifying skin cancer will enable patients to access necessary treatment more quickly.

According to current estimates, one in five Americans will develop skin cancer in their lifetime. The three most common skin cancers are basal cell carcinoma (BCC), squamous cell carcinoma (SCC), and melanoma, the most dangerous form of skin cancer because of its tendency to spread.

If caught early, skin cancer is highly treatable, but it makes early diagnosis crucial. Until now, detection has relied on the naked eye or magnified visual examination of skin lesions, which is dependent upon clinical training and the subjective judgment of primary care physicians (PCPs). However, the FDA recently upped the detection game, granting clearance to DermaSensor, the first AI-powered device to detect all three common skin cancers in real time.

“We are entering the golden age of predictive and generative artificial intelligence in healthcare, and these capabilities are being paired with novel types of technology, like spectroscopy and genetic sequencing, to optimize disease detection and care,” said Cody Simmons, co-founder and CEO of DermaSensor. “Equipping PCPs, the most abundant clinicians in the county, to better evaluate the most common cancer in the country has been a major, long-standing unmet need in medicine. While dozens of companies have attempted to address this problem in recent decades, we are honored to be the first device cleared by the FDA that provides PCPs with an automated tool for evaluation of suspicious lesions.”

It's important to pause here to explain the difference between ‘FDA approved’ and ‘FDA cleared’. Medical devices intended for human use fall into three categories. Class III are complex, implanted devices and products, like pacemakers and breast implants. They require FDA approval, meaning their benefits outweigh the known risks for their intended use, proven using data from clinical trials. Lower-risk devices and products for external use fall into Class I or II (for example, the ECG app for the Apple Watch is in Class II). These devices are ‘cleared’ rather than approved, meaning the FDA has allowed a device to market because it’s “substantially equivalent” (in terms of safety and efficacy) to another legally marketed device.

The tip of the DermaSensor device uses elastic scattering spectroscopy (ESS), a process that evaluates how photons scatter when reflected off different cellular structures. Given malignant skin lesions’ different cellular and sub-cellular make-up, they’ve been reported to scatter light differently from benign lesions. DermaSensor’s built-in AI uses these spectroscopic images to provide physicians with information to help them assess skin lesions, a process explained in the video below.

How DermaSensor Works


The FDA’s clearance was based on clinical trials evaluating DermaSensor’s efficacy. In a study led by the Mayo Clinic across 22 centers in the US and Australia and published in the Journal of Clinical and Aesthetic Dermatology, researchers tested the device on 1,005 patients with, on average, one or two skin lesions. Before the lesions were biopsied, PCPs predicted which ones would be malignant. The DermaSensor device had an overall sensitivity of 95.5% for detecting malignancy – sensitivity of 87.5% for melanoma, 97.8% for BCCs and 98.7% for SCCs – compared to the PCPs’ overall sensitivity of 83.0%.

In an accompanying clinical validation study appearing in the same journal, 108 PCPs evaluated 50 skin lesions (25 malignant, 25 benign) with and without the device. The DermaSensor device was found to decrease the number of missed skin cancers from 18% to 9%. Additionally, physicians reporting high confidence in their evaluations increased from 73.0% to 81.6% when they used the device.

Better identifying skin cancer in the primary care setting will accelerate patient access to necessary treatment. In addition to improving primary care, given the device’s accuracy, DermaSensor is expected to improve PCPs’ collaboration with dermatologists by streamlining the referral system.

Source: DermaSensor

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"Molecular jackhammers" kill cancer by busting through cell walls
Michael Irving, January 28, 2024

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An artist's illustration of the "molecular jackhammers" busting open cancer cells under infrared light Texas A&M Engineering

Scientists have demonstrated an intriguing new technique to treat cancer – “molecular jackhammers” that latch onto cancer cells, then vibrate vigorously to kill them when activated by infrared light.

Chemotherapy and radiation therapy are currently our most effective treatments for cancer, but they have a shotgun effect, damaging healthy cells all through the body. Worse still, some cancers can develop resistance to these attacks, leaving few other options.

But physical attacks are much harder, if not impossible, for cells to develop resistance to. And that’s the goal with the molecular jackhammers developed by researchers at Texas A&M, Rice University and the University of Texas-MD Anderson Cancer Center.

These jackhammers are actually aminocyanine molecules. Their positive charge means they’re attracted to the negative charge of the cancer cells’ outer layers, and once they’re stuck on, infrared light excites electrons in the molecules, causing them to vibrate extremely quickly. A couple of minutes of this is enough to rupture the cell membrane, killing the cancer through necrosis.

In tests, the molecular jackhammers successfully killed off 99% of human melanoma cells in a lab dish. Experiments in live mice with melanoma also resulted in 50% of the animals becoming completely cancer-free.

It might sound like a bad idea to have tiny little jackhammers killing cells in your body, but the important thing to note is that they require infrared light to activate. That means they shouldn’t do any damage if they were to find their way into healthy tissue.

While there’s still plenty of work to do before this could become a practical treatment, it’s an intriguing proof-of-concept. The team says it should be safer and less expensive than radiation, chemotherapy or other experimental techniques like photothermal therapy. The lattermost involves particles or wires of gold or other metals, which can be heated up with lasers to kill tumors.

The new study was published in the journal Nature Chemistry. NB! Por subscripción.

Source: Texas A&M

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New drug triggers "calcium storm" to choke cancer cells to death
Michael Irving, January 29, 2024

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Scientists have developed a method to kill cancer by flooding its cells with calcium Depositphotos

No matter how important something is, too much of anything is bad for you. Scientists have now put that principle to work to kill cancer, with a new drug that causes calcium to build up and choke the tumor to death.

Calcium ions are crucial messengers in biological cells, and play a key role in keeping the energy-producing mitochondria functioning. They travel in and out of cells through channels that open and close with precise triggers to maintain exactly the right balance. If there’s too much calcium, the cell can suffocate. Now, scientists in South Korea and China have developed a drug that can cause a “calcium storm” inside cells on demand, and shown how to use it to fight cancer.

The drug is made up of silica nanoparticles containing a dye called indocyanine green. Tumors recognize silica and transport the nanoparticles inside the target cells, and once there, the dye is activated by near-infrared light. That sets off a two-pronged attack: first it produces molecules called reactive oxygen species (ROS) that open a calcium channel in the cell’s outer membrane. At the same time, it heats up, which causes a calcium-storing organelle inside the cell to open its floodgates.

Imagen
The graphical abstract of the journal article, illustrating the two-pronged attack of the new drug Angewandte Chemie

The technique proved effective in lab experiments on human cancer cells in a dish. Mouse tests followed, which showed that the drug accumulated in the tumors. When the researchers shone near-infrared light on it, the drug went to work and left the mice tumor-free after a few days.

While there’s still plenty more work to be done before this could be trialed in humans, the team says that the basic mechanism of activating ion channels could be investigated for a range of potential therapies.

The research was published in the journal Angewandte Chemie.
Source: Wiley Online Library

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CERN's particle accelerator tech is turned on brain tumors
David Szondy, March 07, 2024

Shifting from giant accelerators 26 km (16 miles) across to brain surgery theaters, a particle detector first developed by physicists at CERN is being used by scientists in Germany to treat brain tumors with greater precision and safety.

Destroying head and neck tumors is relatively simple. You dose them with the right chemicals or blast them with powerful enough radiation, and job done. The problem is figuring out how to kill the cancer cells without killing the patient.

One effective way of treating such tumors is by using ion beams. Accelerating charged particles to three quarters of the speed of light, they can penetrate as far as a foot into living tissue. To protect healthy cells, the conventional technique is to move the ion projector in a curve with the tumor centered at the focus. This way, the tumor is continually bombarded while the healthy tissue is only slightly exposed.

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Preparing a patient for ion beam therapy CERN

It's a simple and effective method, but it's far from perfect, especially when the tumor is in the brain. In such a situation, there's a real danger of exposing neighboring healthy cells to secondary radiation caused by the ion beam hitting tissues, which can result in memory loss, damage to the optic nerve, and other problems.

To minimize this, X-ray computed tomography (CT) scans can precisely map the location of the tumor to guide the surgeon in setting up the treatment. Unfortunately, a scan taken before the operation may be inaccurate because the brain has shifted about in the skull since then.

To compensate for this, researchers from the German National Center for Tumor Diseases (NCT), the German Cancer Research Center (DKFZ), and the Heidelberg Ion Beam Therapy Center (HIT) at Heidelberg University Hospital used a new imaging device built by Czech company ADVACAM that incorporates the Timepix3 pixel detector developed at CERN.

Imagen
The Timepix3 chip CERN

Designed to work with both semiconductor detectors and gas-filled detectors, the Timepix3 is a general-purpose integrated circuit that can take sparse detection data and provide outputs with high resolution over a short time. This allows the ADVACAM to use the secondary radiation from the ion beam to update the tissue maps by using the radiation as a tracking beacon.

"Our cameras can register every charged particle of secondary radiation emitted from the patient's body," said Lukáš Marek from ADVACAM. "It's like watching balls scattered by a billiards shot. If the balls bounce as expected according to the CT image, we can be sure we are targeting correctly. Otherwise, it's clear that the 'map' no longer applies. Then it is necessary to replan the treatment."

The idea is that these updates will better target the tumor while reducing the amount of unwanted radiation the patient is exposed to while hitting the tumor with higher levels of radiation.

At the moment, the detector requires interrupting the treatment to allow for replanning. However, later phases of the program will include the ability to correct the beam path in real time.

"When we started developing pixel detectors for the LHC we had one target in mind – to detect and image each particle interaction and thereby help physicists to unravel the secrets of Nature at high energies," says Michael Campbell, Spokesperson of the Medipix Collaborations. "The Timepix detectors were developed by the multidisciplinary Medipix Collaborations whose aims are to take the same technology to new fields. Many of those fields were completely unforeseen at the beginning and this application is a brilliant example of that."

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Avance clave contra el glioblastoma: una nueva terapia logra reducir el tumor cerebral de tres pacientes en solo unos días
C. Amanda Osuna, INFOBAE, 15 Mar, 2024

El glioblastoma es el tipo de cáncer cerebral más mortal y que se origina a partir de células astrocíticas. Se trata de un tumor altamente invasivo, capaz de crecer rápidamente y cuya extirpación suele ser compleja. Dada su localización, puede perjudicar gravemente el tejido cerebral circundante. En cuanto a los síntomas del glioblastoma, pueden incluir dolores de cabeza persistentes, náuseas, vómitos, visión borrosa, convulsiones y cambios en la función cerebral, según la Clínica Mayo.

El dueño de un bar se salta la ley, ofrece a una camarera un contrato de 48 horas semanales y le dice que es así para cobrar más
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Pese a que no existe una cura y el tratamiento disponible apenas proporciona unos meses más de esperanza de vida, en los últimos años se han logrado avances significativos en la lucha contra el glioblastoma. Ahora, un grupo de investigadores del Mass General Cancer Center en Boston (Estados Unidos) ha desarrollado una nueva terapia celular que es capaz de remitir este tumor cerebral en pocos días.

Según mostraron los escáneres cerebrales de uno de los pacientes del estudio, el glioblastoma de un hombre de 72 años experimentó una reducción casi completa. Otros dos participantes de la investigación también tuvieron resultados positivos en la remisión de su tumor, aunque no al mismo nivel. Lo más impresionante de esta nueva terapia es que los beneficios pudieron observarse a los pocos días de recibir el tratamiento, según los resultados publicados en el The New England Journal of Medicine. Aunque meses después el tumor se volvió recurrente en estos pacientes, los resultados preliminares de esta innovadora terapia siguen motivando al equipo para encontrar una estrategia que perpetúe la durabilidad del tratamiento.

Para desarrollarlo, los científicos optaron por basar la terapia en el propio sistema inmune del paciente, llamado CAR-T. Como explica la Sociedad Americana del Cáncer, las terapias CAR-T, o terapias de células T con receptores quiméricos de antígenos, son un tipo de tratamiento innovador en inmunoterapia celular utilizado en el tratamiento de ciertos tipos de cáncer, como linfomas, leucemias y mieloma múltiple. Estas terapias implican la modificación genética de las células T del paciente para que puedan reconocer y atacar las células cancerosas.

Este enfoque se considera efectivo en pacientes que no responden a tratamientos convencionales y ha demostrado altas tasas de respuesta en ciertos tipos de cáncer hematológico, por lo que los científicos esperan que el glioblastoma sea una de ellas. La terapia CAR-T es un procedimiento complejo que implica la extracción de células T del paciente, su modificación genética en laboratorio y su posterior infusión para combatir las células cancerosas. Es importante destacar que estas terapias representan un avance significativo en el tratamiento del cáncer, especialmente para aquellos pacientes que no han respondido a otras opciones terapéuticas.

La presencia del glioblastoma en nuestro país
Según los datos disponibles a partir de la OMS para España, las neoplasias cerebrales malignas, como el glioblastoma, tienen una incidencia de 7.9 por cada 100.000 habitantes. El glioblastoma es el tumor cerebral más frecuente y agresivo del sistema nervioso central, con una incidencia que varía entre 0.59 y 3.69 por cada 100.000 habitantes por año. Es decir, de media, unos 1.300 casos al año en nuestro país.

https://www.infobae.com/espana/2024/03/ ... unos-dias/
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New lung cancer pill produces “unprecedented” results in human trial
Paul McClure, 03/06/2024

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A clinical trial of a new lung cancer pill has produced remarkable results/Depositphotos

Lung cancer is the number one cause of cancer-related deaths worldwide. A trial of a new anti-cancer drug has found that five years after treatment, 60% of patients with a very common form of the disease are still alive, and the cancer has not progressed.

The protein anaplastic lymphoma kinase (ALK) helps control cell growth. It’s made by the ALK gene, which can be rearranged by some cancers, including non-small cell lung cancer (NSCLC), causing the cancer to grow and spread. One of the two main types of lung cancer – the other is small cell lung cancer – NSCLC accounts for around 80% to 85% of lung cancers, with ALK-positive tumors occurring in about 3% to 5% of those cases. ALK-positive NSCLC is typically more aggressive and seen in younger people with a light or non-smoking history.

Lorlatinib is a third-generation ALK inhibitor, the newest in a class of drugs that are the standard first-line treatment for patients with ALK-positive NSCLC. A recent international clinical trial led by the Peter MacCallum Cancer Center (Peter Mac) in Melbourne, Australia, assessed the drug’s effect on long-term disease progression in patients with advanced ALK-positive NSCLC. The results were remarkable.

“To our knowledge, these results are unprecedented,” said Peter Mac’s Professor Ben Solomon, the study’s lead and corresponding author, in an interview with The Guardian.

In the Phase III trial, 296 patients with previously untreated, advanced ALK-positive NSCLC were randomly assigned to receive either lorlatinib or crizotinib, a first-generation ALK inhibitor sold as Xalkori. Lorlatinib is given as a once-a-day tablet, while crizotinib is given twice daily. The study’s primary endpoint was progression-free survival; the key secondary endpoint was overall survival. Another secondary endpoint was whether the cancer had metastasized to the brain.

Five years after treatment, 60% of patients given lorlatinib were still alive without signs of disease progression, compared to 8% of patients on crizotinib. There was also an 81% reduction in the risk of cancer progression or death and a 94% reduction in the progression of brain metastasis compared to crizotinib.

The current trial was an update on follow-up at the three-year mark, which showed similar progression-free survival and brain progression rates.

“This updated analysis shows that lorlatinib helped patients live longer without disease progression, with the majority of patients experiencing sustained benefit for over five years, including nearly all patients having protection from progression of disease in the brain,” Solomon said

Consistent with the data from previous trials, Lorlatinib was associated with a higher incidence of adverse events than crizotinib, 77% versus 57%, mostly due to increased blood lipids (cholesterol and triglycerides). However, cardiovascular adverse events were similar between the treatment groups. Adverse events related to lorlatinib were manageable with a dose reduction without affecting the drug’s efficacy. The progression-free survival rates and time-to-brain progression were similar in patients whose dose was reduced within the first 16 weeks and those who didn’t take a reduced dose.

After five years of follow-up, the study’s findings represent the longest progression-free survival data ever reported with any single-agent targeted treatment in advanced NSCLC and across all metastatic solid cancer tumors.

“These improvements in outcomes for patients with ALK-positive NSCLC represent a remarkable advancement in lung cancer,” said Solomon.

The trial results were presented at the 2024 American Society of Clinical Oncology (ASCO) annual scientific meeting, currently being held in Chicago, and published simultaneously in the Journal of Clinical Oncology.

Source: Peter MacCallum Cancer Centre

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El artículo se basa (al menos en parte) en información del fabricante.

Melanoma recurrence risk cut by 49% by new vaccine/existing drug combo
Paul McClure, June 03, 2024

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Combining a new melanoma vaccine with an existing drug significantly reduced the risk of the cancer recurring Depositphotos

Results from human trials coupling a new melanoma vaccine with an existing cancer drug showed that, at the three-year mark, the combination treatment reduced the risk of melanoma recurring by 49% and the risk of it spreading by 62%.
According to the Melanoma Research Alliance, the number of new invasive melanoma cases diagnosed annually in the US increased by 27% in the 10 years since 2013. Advanced melanoma can be very hard to treat, and survival very much depends on when the cancer is detected.

From diagnosis, the five-year relative survival rate for localized, early melanoma is over 99%; for melanoma that has spread regionally to nearby lymph nodes and vessels (stage III), it’s 68%; and for melanoma that has spread to distant sites like the brain, lungs, and gut (stage IV), it's 30%.

Biopharmaceutical companies Moderna, Inc. and Merck – known as MSD outside of the US and Canada – have announced the results of Phase IIb of the KEYNOTE-942 study, a clinical trial evaluating the longer-term effectiveness of combining a new melanoma vaccine with an existing anti-cancer immunotherapy drug.

The vaccine, developed by Moderna and called mRNA-4157 (V940), was given in combination with Keytruda (pembrolizumab), Merck’s anti-PD-1 therapy, to 157 patients with high-risk (stage III-IV) melanoma that had been surgically removed. Both boost the immune system’s cancer-fighting abilities. The vaccine is an individualized neoantigen therapy (INT), meaning that it uses the unique DNA signature of a person’s tumor to create a treatment that helps their immune system produce an anti-tumor response. Keytruda blocks the PD-1 pathway that cancer uses to hide in the body, helping the immune system detect and fight cancer cells.


Individualized neoantigen therapies: Exploring one medicine for one patient

After a follow-up of almost three years (median follow-up 34.9 months), the combination treatment reduced the risk of cancer recurrence or death by 49%, compared to treatment with Keytruda alone. Further, compared to Keytruda alone, treatment with both drugs reduced the risk of developing distant metastases or death by 62%.

“The sustained improvements in recurrence-free survival and distant metastasis-free survival observed at approximately three years in the KEYNOTE-942/mRNA-4157-P201 study provide further support of the potential of mRNA-4157 (V940) in combination with Keytruda to help patients with resected high-risk melanoma,” said Dr. Marjorie Green, senior vice president and head of oncology, global clinical development at Merck. “We look forward to building on our legacy of turning breakthrough science into medicines that may have a meaningful impact on patient’s lives as we continue advancing our broad clinical development program evaluating this novel approach with Moderna.”

The most common adverse effects attributed to the combination of mRNA-4157 (V940) and Keytruda were fatigue (60.6%), injection site pain (56.7%), and chills (49%).

The current Phase IIb trial could be considered a ‘mini-Phase III’ trial designed to provide data on the treatment’s effectiveness. Merck and Moderna have now commenced Phase III randomized clinical trials proper to evaluate the mRNA-4157 (V940) vaccine in combination with Keytruda in patients with resected high-risk melanoma and non-small cell lung cancer, the most common type of lung cancer. The companies also, in 2024, began Phase II trials of the combination treatment in patients with renal cell carcinoma, a type of kidney cancer, and bladder cancer.

The researchers presented their trial results at the 2024 American Society of Oncology (ASCO) annual scientific meeting, currently being held in Chicago.

Source: Moderna
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100% of cancer patients cured long-term in 'remarkable' human trial
Bronwyn Thompson, 05/06/2024

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High hopes for the use of dostarlimab-gxly in successfully 'reversing' a type of colorectal cancer, with hopes it will be able to target other forms Depositphotos

In what researchers have called an "unprecedented" response, a new drug that treats locally advanced rectal cancer has shown to have completely eradicated tumors in all 42 patients who took part in the Phase II trial.

The drug, Jemperli (dostarlimab-gxly), had earlier shown great potential for eliminating mismatch repair deficient (dMMR) cancers, which make up 5-10% of colorectal cancers. Following the Phase II trial, the first 24 patients assessed showed a "sustained complete clinical response" – no cancer evident – after an average of 26.3 months.

"These findings demonstrate the potential of dostarlimab-gxly as a novel approach to treating locally advanced dMMR rectal cancer that leads to durable complete tumor regression without the need for life-altering treatment," said Dr Andrea Cercek, researcher and oncologist at the Memorial Sloan Kettering Cancer Center (MSK). "As a clinician, I’ve seen firsthand the debilitating impact of standard treatment of dMMR rectal cancer and am thrilled about the potential of dostarlimab-gxly in these patients.”

The drug is a hugely promising first-line treatment option, bypassing the need for chemotherapy and radiation. Right now, while traditional treatment is effective, it's incredibly invasive and impacts long-term quality of life. And ultimately, a third of patients will see their cancer metastasize and become terminal.

Those who do undergo surgery often experience life-long life-changing impacts, including bowel, urinary and sexual dysfunction, as well as secondary cancers and infertility.

“We wanted to see if we could make a tumor with the MMR(d) mutation recede and eventually disappear using only immunotherapy to spare patients these life-altering consequences of standard treatment," Dr Luis Diaz Jr said last year, after preliminary trial research showed how effective this drug was at targeting the cancer.

Unlike chemotherapy, dostarlimab-gxly is a programmed death receptor-1 (PD-1)-blocking monoclonal antibody, which enters the body and binds to the protein PD-1 T cells, encouraging these immune cells to attack cancer cells. While still in its early stages before clinical use, it's already been hyped up as a 'wonder drug' for successful, non-invasive cancer treatment.

Last year, the drug was approved by the FDA as a complementary treatment alongside chemotherapy for endometrial cancer. The pharmaceutical company behind Jemperli, GSK, will now undertake studies on other types of colorectal cancers, hoping for similar impactful results.

“The data showing no evidence of disease in 42 patients is remarkable,” said Hesham Abdullah, GSK Senior Vice President. “These results bring us one step closer to understanding the potential of dostarlimab-gxly in this curative-intent setting for patients with dMMR locally advanced rectal cancer. We look forward to evaluating dostarlimab-gxly in certain colorectal cancers in our ongoing AZUR-1 and AZUR-2 registrational studies.”

In a statement, GSK said patients didn't experience side-effects above grade three, with most experiencing mild or moderate adverse reactions. The company noted that the drug's safety and tolerance is "consistent with the known safety profile of the agent."

The results of the long-term follow-up examinations were presented at the 2024 American Society of Clinical Oncology (ASCO) annual meeting in Chicago this week.

Source: GSK
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Cancer-fighting antibodies inject chemo directly into tumor cells, upping effectiveness
Berkeley Lovelace Jr., 02/06/2024

Oncologists have grown increasingly excited about "antibody drug conjugates," which allow for the use of more potent chemotherapy agents with fewer side effects.

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Antibody drug conjugates are designed to attack only cancer cells — not other healthy cells in the body — and inject a potent dose of chemotherapy.Leila Register / NBC News; Getty Images

By attaching a chemotherapy drug to an antibody, doctors are able to deliver more potent cancer-fighting medicines directly into tumor cells, all while causing fewer side effects.

The chemotherapy-antibody combinations, known as antibody drug conjugates, have been described as both heat-seeking missiles and Trojan horses for cancer cells, designed to specifically home in on a patient’s tumor cells and trick them into engulfing the antibodies, along with their deadly payload.

The approach isn’t entirely new: The first antibody drug conjugate was approved by the Food and Drug Administration in 2000 to treat acute myeloid leukemia, a type of blood cancer. Since then, other approvals have followed, for treatments targeting cancers of the breast, lung, cervix and ovaries, and more than 100 are in clinical development, according to a review in the journal Cancers.

Oncologists, however, have become increasingly enthusiastic about the treatments in recent years, as researchers have pinpointed new, better targets that allow the drugs to take down cancer cells with more accuracy.

“There’s been an explosion of these agents over the past couple of years and we have a ton of them in clinical trials right now,” said Dr. Erika Hamilton, a medical oncologist and the director of breast cancer and gynecologic cancer research at Sarah Cannon Research Institute in Tennessee.

New research on two different antibody drug conjugates, presented Sunday at the American Society of Clinical Oncology (ASCO) conference in Chicago, found that the treatments helped patients with multiple myeloma and breast cancer live longer without their cancers progressing further.

“It’s really starting to come into its own,” Dr. Hatem Soliman, a medical oncologist at Moffitt Cancer Center in Tampa, Florida, said of the research. “It appears to be here to stay.”

How it works
Roughly 2 million people in the U.S. will be diagnosed with cancer this year, according to the National Cancer Institute. Chemotherapy will be the standard treatment for many of those patients.

Chemotherapy drugs work by killing cancer cells. While often effective, they can also come with major side effects because they’re unable to discriminate between cancer cells and healthy ones.

Antibody drug conjugates, on the other hand, are designed to attack only cancer cells, thanks to the addition of specialized monoclonal antibodies that seek out specific targets on the cancer cells.

“It’s kind of like a Trojan horse,” said Dr. Giuseppe Curigliano, co-chair of the experimental therapeutics program at the European Institute of Oncology in Italy. “The antibody can bind specifically to a target region, and once there is the binding, you can bring the chemotherapy into the cancer cells.”

The approach also means that much more of the drug gets inside of the tumor cells.

“You’ve delivered chemo inside the cancer cell,” said Dr. Julie Gralow, ASCO’s chief medical officer and executive vice president. “You can get very high levels of chemo inside the cancer cell, levels that in many cases with these drugs you couldn’t achieve if you just gave the drug by itself into the vein.”

Delivering the drug directly into the cell allows doctors to use more potent forms of chemotherapy, including some that were previously found to be too toxic to patients.

These were drugs that “were really toxic to the tumor, but they were also really toxic to the patient,” Gralow said. “But now, you can put them on an antibody and you can deliver them in a way where you can still get a really high level in the cancer cell and lower level out in the rest of the body, and you can start using them.”

But this approach doesn’t eliminate side effects entirely, she added. Patients can still experience common chemotherapy side effects including hair loss and low white blood cell counts.

For Rose Fish, 79, of The Villages, Florida, the side effects were more manageable than with standard chemotherapy, including less vomiting and hair loss.

Fish was diagnosed with breast cancer in 2011. After surgery, chemotherapy and radiation, she was cancer-free until 2020, when she learned that the cancer had come back and spread to her liver and bones.

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Rose Fish said she's noticed fewer side effects from an antibody drug conjugate compared to traditional chemotherapy. Courtesy Rose Fish

When her cancer stopped responding to traditional chemotherapy, her oncologist, Soliman of Moffitt Cancer Center, explored the option of using an antibody drug conjugate.

The treatment, Soliman said, led to a major improvement in Fish’s disease, and she’s been in stable condition.

“She’s been a good example of how ADCs are really changing the way we treat breast cancer and other diseases,” he said, using an abbreviation for antibody drug conjugates.

Fish said she has been feeling great on the new treatment.

“I played, two weeks ago, 18 holes of golf, so it’s been pretty darn good,” she said.

‘A clear, clear positive signal’
Fish later learned that she had a subtype of breast cancer called HER2-low, a recently identified form of the disease.

Previously, breast cancers had been classified as being either HER2-positive or HER2-negative, depending on whether their tumor cells carried the HER2 molecule. However, up to 60% of breast cancers have low levels of the molecule, including about half of those advanced breast cancers.

One of the studies presented Sunday at the ASCO conference found that Enhertu, an antibody drug conjugate from drugmakers ​​AstraZeneca and Daiichi Sankyo, extended the length of time patients with HER2-low breast cancer went without their tumors getting worse by about five months compared to those who got chemotherapy.

“The study clearly demonstrated that trastuzumab is better than standard chemotherapy,” said senior author Curigliano, of the European Institute of Oncology, using the technical name for the treatment. “There is a dramatic impact on the lives of patients.”

In April, the Food and Drug Administration expanded Enhertu’s approval, saying the treatment could be used for any type of cancer with the HER2 molecule. The drug was already approved for breast and lung cancer, but now can be used for cancers including stomach and colon, which can carry HER2.

Results from another study compared the antibody drug conjugate Blenrep, from GlaxoSmithKline, to a more common treatment regimen for multiple myeloma.

The phase 3 clinical trial included more than 300 patients, all of whom got pomalidomide and dexamethasone, two drugs often used together to treat multiple myeloma. Roughly half were also given Blenrep, and the other half got bortezomib, a drug that’s been shown to be successful in delaying progression of the disease and is approved in the U.S.

The researchers, led by Dr. Suzanne Trudel, a professor of medicine at the University of Toronto, found that after 12 months, 71% of the people who got the Blenrep combination therapy saw no progression of their cancer, compared to 51% of the patients in the other group.

After about 22 months, she said, more than half of the patients in the Blenrep group still hadn’t seen any progression. The 50% mark for progression was hit at around 13 months in the other group.

“A clear, clear positive signal,” Trudel said. “I think this is really encouraging for patients with myeloma, which is an incurable disease.”

Blenrep has had a short but rocky history: It was granted fast-track approval by the FDA in 2020, but two years later, the agency asked GlaxoSmithKlein to pull the drug from the market after a phase 3 trial failed to show that it worked better than an existing treatment.

Gralow said the new findings could persuade the FDA to approve the drug once again.

A ‘warhead’ for cancer
The results add to excitement that the treatments could one day be the standard approach for chemotherapy, said Sophia Karagiannis, a translational cancer immunologist at King’s College London.

Karagiannis published a study in the journal Clinical Cancer Research in May that found researchers were able to use a tailor-made antibody drug conjugate for triple-negative breast cancer, one of the most difficult-to-treat forms of the disease.

“I would describe them as smart warheads,” she said. “I think the future will be that we will be able to combine chemotherapy with many of these smart drugs.”

The focus for many oncologists right now is figuring out how to make the drugs attack cancer cells more precisely as well as making the effects last longer.

“ADCs are in some ways more complicated than chemotherapies in that they are more complex molecules, they’re bigger,” Karagiannis said. “We are trying to understand how well we can make those molecules so that they can be more stable.”

Dr. Dale Shepard, a medical oncologist with the Cleveland Clinic, said because the treatments are so effective at attacking cancer cells, patients often report fewer side effects and also have to come to get their infusions less often — about once every 28 days versus every one or two weeks with traditional chemotherapy.

The treatments are often more expensive than traditional chemotherapy, however.

Hamilton, of the Sarah Cannon Research Institute, said that some antibody drug conjugates are already being widely used, even as a first-line chemotherapy treatment, as opposed to waiting until after traditional chemotherapy isn’t successful.

“Getting these drugs to patients earlier is already underway,” Hamilton said. “They are for sure going to have a firm role in oncology.”

https://www.nbcnews.com/health/health-n ... rcna153773
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