Cancer News and Discussions

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Novel T cell receptor therapy shows early anti-tumor activity

by University of Texas M. D. Anderson Cancer Center
https://medicalxpress.com/news/2023-01- ... tumor.html
Afamitresgene autoleucel (afami-cel; formerly ADP-A2M4), an adoptive T cell receptor (TCR) therapy targeting the MAGE-A4 cancer antigen, achieved clinically significant results for patients with multiple solid tumor types in a Phase I clinical trial led by researchers at The University of Texas MD Anderson Cancer Center.

The outcomes, published today in Nature Medicine, were especially noteworthy in the subgroup of patients with synovial sarcoma, where afami-cel achieved an objective response rate of 44% compared to the overall response rate of 24% across all cancer types. Initial data from this trial were presented at the 2020 American Society of Clinical Oncology (ASCO) Annual Meeting.

According to principal investigator David S. Hong, M.D., professor of Investigational Cancer Therapeutics, these early results demonstrate a proof-of-concept for this novel cell therapy approach in solid tumors.

"These high response rates are significant because patients with synovial sarcoma really have very few options after high-dose chemotherapy with ifosfamide," Hong said. "The overall toxicity from afami-cel was manageable, and we saw evidence of early activity in other cancer types. These results suggest this is an approach with the potential to work in solid tumors where there are currently no approved cellular therapies."
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weatheriscool
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One of the causes of aggressive liver cancer discovered: A 'molecular staple' that helps repair broken DNA
https://medicalxpress.com/news/2023-01- ... taple.html
by The Spanish National Cancer Research Centre
Error-correcting mechanisms are very important for cells, because with all the cellular activity constantly going on, malfunctions arise all the time. But when it comes to killing cancer cells, it is in the cells' best interest to induce errors. Radiotherapy and chemotherapy can cause cellular defects by breaking the DNA of the cells. However, some tumor cells have an exceptionally efficient DNA repair machinery that allows them to evade cancer treatment.

In a paper published in Cell Reports, Óscar Llorca of the CNIO, Fernando Moreno-Herrero of the CNB and Puri Fortes of the CIMA-University of Navarra have now revealed the workings of one of these extraordinary repair systems: a molecular staple that has been shown in action for the first time using a new nanotechnology technique.
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Scientists develop a peptide that targets lung tumors and delivers therapeutics inside cells
https://medicalxpress.com/news/2023-02- ... utics.html
by SRI International

Lung cancer claims more lives each year than any other type of cancer worldwide. According to the World Health Organization, an estimated 1.8 million people died of lung cancer in 2020. Current treatments rely on one of two avenues: generalized chemotherapy that inflicts harsh side effects on cancer patients, or targeting of tumors with very specific mutations that may not apply to many patients—both of which make fighting the disease challenging.

Researchers at SRI International have designed and optimized a new peptide—a molecule that contains two or more amino acids—to act as a delivery vehicle for drugs to treat non-small cell lung cancer, which accounts for the majority of lung cancer cases. This peptide, highlighted in a recent study published in Nature Communications Biology, can carry large anti-cancer drugs and successfully target cancerous cells, binding to them and triggering a process to draw the peptide and its cargo inside.

"With our peptides, we can start to deliver large cargos inside of a cell that couldn't otherwise pass through the cell membrane," said Kathlynn Brown, vice president of drug delivery systems at SRI's Bioscience division and lead author on the paper. "It opens the door to basically dragging therapeutics into the inner workings of tumor cells while avoiding healthy cells, minimizing the potential side effects."

Currently, most similarly targeted cancer drugs are delivered by antibodies, which bind to specific receptors on the surface of a cancer cell. But there are several advantages to using peptides instead of antibodies. First, peptides are significantly smaller molecules, which means that they can penetrate deeper into a tumor. Second, peptides can be put together chemically, while antibodies must be produced biologically in cells. The chemical process is faster, less expensive and gives researchers more precise control over the final result.

"Because we make them chemically, we have a lot of flexibility in how we incorporate the drug," Brown said. "We can put on whatever drug or cargo we want, we will know exactly where it is, and we can modify that with tools we have in the lab."

To find a peptide with the right set of traits, Brown and her colleagues use a proprietary selection process to sift through a library of billions of potential options. In this case, they needed a peptide that could successfully seek out and bind to cancer cells while leaving healthy cells alone; could trigger biological processes to rapidly draw the peptide and its cargo into the cell; and wouldn't degrade while circulating through the body.
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Scientists identify a gene signature to assess cancer risk in people
https://medicalxpress.com/news/2023-02- ... eople.html
by The Wistar Institute
In a paper published in PNAS, Maureen Murphy, Ph.D., Deputy Director of Wistar's Ellen and Ronald Caplan Cancer Center and Ira Brind Professor and Program Leader in the Molecular & Cellular Oncogenesis Program, and team have identified a gene signature that accurately predicts the functioning of P53 variants, important information to assessing cancer risk and optimizing choices for cancer therapeutics.

"There are so many genetic variants of P53," explained Murphy. "A lot of P53 variants are classified as having uncertain significance with current methods of testing. This does not help people determine whether they have increased cancer risk. The signature we identified does."

The Murphy lab monitored differences in activity in mutant and normal p53 proteins to determine any genetic markers that would flag if a p53 variant is functioning less than normal. In collaboration with Andrew Kossenkov, Ph.D., assistant professor in Wistar's Vaccine and Immunotherapy Center, the research team used machine learning to identify a gene signature that consistently and accurately predicted the difference between a normal functioning or benign p53 and a lower functioning variant of the protein.
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Simple low-dose aspirin may boost ovarian cancer survival

by QIMR Berghofer
https://medicalxpress.com/news/2023-02- ... arian.html
New QIMR Berghofer research has found that low-dose aspirin may improve ovarian cancer survival.

The study followed more than 900 Australian women newly-diagnosed with ovarian cancer, and asked them how often they used nonsteroidal anti-inflammatory drugs (NSAIDs) such as aspirin.

Lead researcher Dr. Azam Majidi said the women who reported taking NSAIDs at least four days a week in the 12 months after diagnosis, lived longer on average than occasional or non-users. Most of the frequent users were taking daily low-dose aspirin.

"Our findings suggest that frequent NSAID use might improve survival for women with ovarian cancer, regardless of whether they start taking the drugs before or after diagnosis," Dr. Majidi said.

"We found the difference would translate to an average of an extra 2.5 months' survival in the five years post-diagnosis. While this might not sound like a lot, it is significant for ovarian cancer. The disease is often diagnosed at an advanced stage when the prognosis is poor, and treatment options are limited."
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Potential new series of drugs targeting cancer-driving protein BCL6
https://medicalxpress.com/news/2023-02- ... otein.html
by Institute of Cancer Research
Scientists have revealed details of the discovery of new inhibitors of the BCL6 protein, which is involved in driving several cancer types including the blood cancer B-cell lymphoma.

The inhibitors are small molecules that block BCL6's action. With further research they could be developed into drugs to treat a range of cancer types, including blood cancers and solid tumors.

The compounds were discovered by researchers at The Institute of Cancer Research, London, through a multidisciplinary collaboration between assay scientists, medicinal chemists, biophysicists, structural biologists and other scientists at the Center for Cancer Drug Discovery at the ICR.
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CAR-T cell cancer immunotherapy gets personal
https://medicalxpress.com/news/2023-02- ... sonal.html
by Benjamin Boettner, Harvard University
New adoptive T cell therapies—in which T cells, the immune system's natural hunters patrolling the body for foreign adversaries, are retrieved from cancer-riddled patients, super-charged and amplified outside the body, and then infused back into the same patient—are changing the prospects of cancer patients.

Since 2017, when CAR (chimeric antigen receptor)-T cells were green-lighted as the first modified therapeutic cells by the Federal Drug Administration (FDA) to treat leukemia, five similar products have since been approved and more than 20,000 people have been treated with this game-changing immunotherapy.

CAR-T cells are engineered to carry synthetic membrane-spanning receptor molecules that use their outside-facing portion to bind to antigens on cancer cells, which their inside-facing portion responds to by switching on a powerful tumor cell-destroying program. However, not all patients respond equally well to CAR-T cell therapies, and cancer immunologists have been trying to figure out what makes them work well or fail.

Despite a budding understanding of differences between cancer patients' T cells and healthy individuals' T cells, these insights have not been taken into account in CAR-T cell manufacturing processes. All processes use a similar type of stimulation with T-cell specific agonists and general immune-stimulating cytokines to create infusible CAR-T cell products, irrespective of variations in the original T cells' phenotype.
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wjfox wrote: Thu Feb 02, 2023 8:46 am
these types of reports frustrate me because that look at people and assume that dietary patterns are causative in the pattern of disease.

But stop and ask yourself if somebody who eats baloney sandwhiches every day, hotdogs and mac and cheese from a box every weekend, pizza with bacon and pepperoni and fritos with beer on sunday football. with donuts and coffee for breakfast...

what are the odds that those folks have a menial job with high stress that effects their blood pressure and cortisol levels? Do you think they live in areas with lower or higher pollution both in water and air? Does their house have asbestos, lead paint and mold? Do they hire somebody to do their cleaning and thus they are removed from exposure to harsh chemical cleaners in use before they are rinsed away?

What are the sleep patterns, drinking habits, smoking or exercise habits in the population? Is it a study done on americans? Cuz what are the chances that they have regular medical guidance and preventative healthcare?

It's my experience that those who eat more ready meals, live in poverty, in outdated housing, are over worked and over stressed. They self medicate with alcohol and smoking (sometimes tobacco sometimes weed). the air quality and water in their areas are bad and they cannot afford to live anywhere else. And they haven't been to a doctor in 5 years. I'd wager that mucks up the results of cancer statistics a bit.
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