Cancer News and Discussions

weatheriscool
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Scientists retool CAR T cells to serve as 'micropharmacies' for cancer drugs
https://medicalxpress.com/news/2021-12- ... acies.html
by Memorial Sloan Kettering Cancer Center
Immunotherapies called chimeric antigen receptor (CAR) T cells use genetically engineered versions of a patient's own immune cells to fight cancer. These treatments have energized cancer care, especially for people with certain types of blood cancers. Now, scientists at Memorial Sloan Kettering Cancer Center's Sloan Kettering Institute (SKI) have developed new CAR T cells that can do something their predecessors cannot: Make drugs.

Standard-issue CAR T cells are designed in the lab to recognize specific markers on cancer cells. When these CAR T cells are given back to a patient, they proliferate and go on the attack, acting as a kind of "living drug."

Despite their usefulness for treating blood cancers, there are several limitations of current CAR T models. One is that the CAR T cells can only kill cancer cells that contain the marker they are designed to recognize. But it is not uncommon for cancer cells to stop making this marker and thus to "escape" from the therapy.
weatheriscool
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Researchers develop optical biopsy system that detects liver cancer
https://medicalxpress.com/news/2022-01- ... ancer.html
by The Optical Society

Researchers have developed an optical biopsy system that can distinguish between cancerous and healthy liver tissue. The new technology could make it easier to diagnose liver cancer, which is the sixth most common cancer globally.

"The instrument is designed to be compatible with the needles currently used for liver biopsies," said Evgenii Zherebtsov, a member of the research team from Orel State University in Russia. "It could thus one day help surgeons more precisely navigate the biopsy instrument to decrease the number of errors in taking tissue samples that are used for diagnosis."

In the Optica Publishing Group journal Biomedical Optics Express, the researchers report that the optical biopsy system can reliably distinguish between cancerous and healthy cells in mouse models. The system also showed promise in preliminary tests conducted in people with suspected liver cancer.

"Optical biopsy methods like the one we developed make it possible to differentiate healthy and tumor tissues with a high degree of accuracy," said Elena V. Potapova, who was co-first author of the paper with Zherebtsov. "Although our system was specifically designed for use in abdominal surgery, our results show that similar technologies could be useful for other medical applications."
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Vaccine-like mRNA injection can be used to make CAR T cells in the body
https://medicalxpress.com/news/2022-01- ... -body.html
by Perelman School of Medicine at the University of Pennsylvania

An experimental immunotherapy can temporarily reprogram patients' immune cells to attack a specific target via only a single injection of messenger RNA (mRNA), similar to the mRNA-based COVID-19 vaccines, according to a new study from researchers in the Perelman School of Medicine at the University of Pennsylvania.

The researchers, whose work is published today in Science, demonstrated the new approach with an mRNA preparation that reprograms T cells—a powerful type of immune cell—to attack heart fibroblast cells. Heart failure is often driven in part by these fibroblast cells, which respond to heart injury and inflammation by chronically overproducing fibrous material that stiffens the heart muscle, impairing heart function—a condition called fibrosis. In experiments in mice that model heart failure, the reduction in cardiac fibroblasts caused by the reprogrammed T cells led to a dramatic reversal of fibrosis.

"Fibrosis underlies many serious disorders, including heart failure, liver disease, and kidney failure, and this technology could turn out to be a scalable and affordable way to address an enormous medical burden," said senior author Jonathan A. Epstein, MD, chief scientific officer for Penn Medicine and executive vice dean and the William Wikoff Smith Professor of Cardiovascular Research in the Perelman School of Medicine. "But the most notable advancement is the ability to engineer T cells for a specific clinical application without having to take them out of the patient's body."
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Tangled messages: Tracing neural circuits to chemotherapy's 'constellation of side effects'
https://medicalxpress.com/news/2022-01- ... erapy.html
by Georgia Institute of Technology

Severe and persistent disability often undermines the life-saving benefits of cancer treatment. Pain and fatigue—together with sensory, motor, and cognitive disorders—are chief among the constellation of side effects that occur with the platinum-based agents used widely in chemotherapy treatments worldwide.

A new study by Georgia Tech researchers in the lab of Timothy C. Cope has found a novel pathway for understanding why these debilitating conditions happen for cancer patients and why scientists should focus on all of the possible neural processes that deliver sensory or motor problems to a patient's brain—including the central nervous system—and not just the "peripheral degeneration of sensory neurons" that occurs away from the center of the body.

The new findings "Neural circuit mechanisms of sensorimotor disability in cancer treatment" are published in the Proceedings of the National Academy of Sciences (PNAS) and could impact development of effective treatments that are not yet available for restoring a patient's normal abilities to receive and process sensory input as part of post cancer treatment, in particular.
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Blood test helps predict who may benefit from lung cancer screening
https://medicalxpress.com/news/2022-01- ... ening.html
by University of Texas M. D. Anderson Cancer Center
A blood test, combined with a risk model based on an individual's history, more accurately determines who is likely to benefit from lung cancer screening than the current U.S. recommendation, according to a study published today in the Journal of Clinical Oncology led by researchers from The University of Texas MD Anderson Cancer Center.

A personalized lung cancer risk assessment, combining a blood test based on a four-marker protein panel developed at MD Anderson and an independent model (PLCOm2012) that accounts for smoking history, was more sensitive and specific than the 2021 and 2013 U.S. Preventive Services Task Force (USPSTF) criteria. The study included participants from the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial with at least a 10 pack-year smoking history. If implemented, the blood test plus model would have identified 9.2% more lung cancer cases for screening and reduced referral to screening among non-cases by 13.7% compared to the 2021 USPSTF criteria.

"We recognize that a small percentage of people who are eligible for lung cancer screening through an annual low-dose CT scan are actually getting screening. Moreover, CT screening is not readily available in most countries. So, our goal, for many years, has been to develop a simple blood test that can be used first to determine need for screening and make screening for lung cancer that much more effective," said Sam Hanash, M.D., Ph.D., professor of Clinical Cancer Prevention and leader of the McCombs Institute for the Early Detection and Treatment of Cancer. "Our study shows for the first time that a blood test could be useful to determine who may benefit from lung cancer screening."
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Study sets framework for precision surveillance of colorectal cancer
https://medicalxpress.com/news/2022-01- ... ancer.html
by Tom Wilemon, Vanderbilt University Medical Center
A team of Vanderbilt researchers has revealed some of the mechanisms by which polyps develop into colorectal cancer, setting the framework for improved surveillance for the cancer utilizing precision medicine.

Their study, published Dec. 14 in Cell, describes findings from a single-cell transcriptomic and imaging atlas of the two most common colorectal polyps found in humans: conventional adenomas and serrated polyps. They determined that adenomas arise from expansion of stem cells that are driven by activation of WNT signaling, which contributes to the development of cancer, while serrated polyps derive into cancer through a different process called gastric metaplasia. The finding about metaplasia, an abnormal change of cells into cells that are non-native to the tissue, was surprising, the researchers said.

"Cellular plasticity through metaplasia is now recognized as a key pathway in cancer initiation, and there were pioneering contributions to this area by investigators here at Vanderbilt," said Ken Lau, PhD, associate professor of Cell and Developmental Biology, one of the study's corresponding authors. "We now have provided evidence of this process and its downstream consequences in one of the largest single-cell transcriptomic studies of human participants from a single center to date."
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Researchers develop new generation tumor-specific pro-IL-12
https://medicalxpress.com/news/2022-01- ... o-il-.html
by Liu Jia, Chinese Academy of Sciences

Interleukin-12 (IL-12), a potent inducer of cell-mediated immunity, can stimulate the anti-tumor effector functions of the activated T and NK cells for solid tumors rejection. However, clinical administration of IL-12 has been limited because of its short half-life, low efficacy, and dose-limiting systemic toxicity.

In a study published in Science Immunology, Prof. Peng Hua at the Institute of Biophysics of the Chinese Academy of Sciences and Prof. Fu Yangxin at the University of Texas Southwestern Medical Center, and collaborators, developed a new generation IL-12, the pro-IL-12, with low toxicity, tumor restriction, and high anti-tumor efficiency.

The researchers first constructed an IL-12-Fc fusion protein to extend the in vivo half-life of IL-12 and further engineered a pro-IL-12 with the functional site blocked by an MMP-cleavable peptide-linked IL-12 natural extracellular receptor-binding domains. Pro-IL-12 could be reactivated when the linker was cleaved by tumor-enriched MMP14. Systemic treatment with pro-IL-12 resulted in effective tumor control and prolonged mouse survival.
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Cancer therapy using on-site synthesis of anticancer drugs
https://medicalxpress.com/news/2022-01- ... ancer.html
by RIKEN
An international research group at the RIKEN Cluster for Pioneering Research (CPR) has successfully treated cancer in mice using metal catalysts that assemble anticancer drugs together inside the body. Published in the scientific journal Nature Communications, the study is the first report of therapeutic in vivo synthetic chemistry being used to make anticancer substances where they are needed simply by injecting their ingredients through a vein. Because this technique avoids indiscriminate tissue damage, it is expected to have a significant impact on cancer treatment.

Aside from effectiveness at killing cancer cells, a major challenge to cancer chemotherapy is how to mitigate the toxic side effects on the body. Drugs that can damage cancer cells can damage non-cancerous cells as well, and the negative side effects of chemotherapy can cause permanent and debilitating damage. Current methods for reducing these side effects include selective delivery of anticancer drugs to cancer tissue (drug delivery) and conversion of non-toxic compounds (prodrugs) into toxic compounds nearby the cancerous tissue.
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Treatment With Injections of Zika Virus Destroys Brain Tumors in Mice Without Causing Neurological Damage
January 11, 2022

https://www.eurekalert.org/news-releases/939805

Introduction:
(EurekAlert) In a study conducted at the University of São Paulo’s Human Genome and Stem Cell Research Center (HUG-CELL) in Brazil, serial systemic injections of zika virus into mice with brain tumors destroyed the cancer without causing neurological damage or injuring other organs, and increased the animals’ survival rate.

The scientists also injected zika into cerebral organoids, brain-like organs created in vitro using stem cells. The virus not only prevented progression of the tumors but actually reduced their size.

In both the mice and the organoids, cytokines (proteins that regulate the immune response) suppressed tumor growth after treatment, and defense cells migrated to the brain region affected by the tumor, alerting the immune system to its existence.

These results, reported in an article published in a special issue of the journal Viruses, confirm the efficacy and safety of treatment with zika in both models, opening up prospects for the use of virotherapy to treat central nervous system tumors.
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caltrek
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Jonsson Comprehensive Cancer Center Researchers Identify Signaling Mechanisms in Pancreatic Cancer Cells that Could Provide Treatment Targets
January 11, 2022

https://www.eurekalert.org/news-releases/939758

Introduction:
(EurekAlert) Research led by scientists at the Jonsson Comprehensive Cancer Center (JCCC) at UCLA provides new insights into molecular “crosstalk” in pancreas cancer cells, identifying vulnerabilities that could provide a target for therapeutic drugs already being studied in several cancers. This interdisciplinary research was led by a team of JCCC investigators, Dr. Caius Radu, an expert in cancer cell metabolism, and Dr. Timothy Donahue, a pancreas cancer surgeon and an expert in pancreas cancer biology.

“Pancreatic ductal adenocarcinoma, which is highly resistant to current therapies, is expected to become the second most common cause of cancer-related deaths in the United States within this decade,” said senior author Caius Radu, MD, a researcher at Jonsson Comprehensive Cancer Center at UCLA and Professor in the Department of Molecular and Medical Pharmacology at UCLA. “Results of this study increase our understanding of the inflammatory microenvironment within these tumors and suggest targeted pharmacological strategies that could be employed to leverage this hallmark feature of pancreas cancer by current treatments.”

The preclinical research, using tumor cells from patients and cell line-derived xenograft tumors, was published online at Cell Reports on Jan. 11. It centers on STING-driven type I interferon, an immune system signaling molecule that impairs cancer cell proliferation in lab studies but tends to have the opposite effect in clinical practice, where tumor cells adapt to them and often become resistant to treatment with radiation, chemotherapy and immune checkpoint blockade. Interferons are produced in immune and other cells, including some types of cancer cells.

“We determined that a subset of PDAC tumors exhibit an intrinsic interferon response that has not been modeled by standard cell culture conditions. Using several advanced techniques, we found that interferon signaling causes the tumor cells to rely on a specific signaling pathway for survival. However, if we inhibit a protein called ATR, which plays an important role in this signaling pathway, we can cause catastrophic damage to the cancer cells’ DNA and induce programmed cell death,” said Evan Abt, a postdoctoral researcher in Dr. Radu’s lab and co-first author of the article with Thuc Le, adjunct assistant professor in Molecular and Medical Pharmacology, and Amanda Dann, MD, a resident in surgery at the UCLA David Geffen School of Medicine.

Results suggest that new small molecule drugs that inhibit ATR and are being studied for treatment of several cancers, including PDAC, could be used in combination with interferon “amplification” to thwart the tumor cells’ ability to escape.
Don't mourn, organize.

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