Cancer News and Discussions

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weatheriscool
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nsights from our genome and epigenome will help prevent, diagnose and treat cancer

by Garvan Institute of Medical Research
https://medicalxpress.com/news/2021-09- ... ancer.html
In 2020, an estimated 10 million people lost their lives to cancer. This devastating disease is underpinned by changes to our DNA—the instruction manual for all our cells.

It has been 20 years since scientists first unveiled the sequence of the human genome. This momentous achievement was followed by major technological advances that allow us to today read the layers of information of our DNA in enormous detail—from the first changes to DNA that occur as a cell becomes cancerous to the complex microenvironments of advanced tumors.

Now, to accelerate discoveries for cancer patients, we need new ways to bring together the different types of complex data we generate to provide new biological insights into cancer evolution.

For today's issue of Science, my colleagues Professor Toshikazu Ushijima, Chief, Epigenomics Division, National Cancer Center Research Institute (Japan), Prof Patrick Tan, Executive Director, Genome Institute of Singapore and I were invited to review the cancer insights we can currently obtain from analyzing DNA in its full complexity and define the future challenges we need to tackle to yield the next step-changes for patients.
weatheriscool
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Powerful technique details brain tumors' formidable resiliency
https://medicalxpress.com/news/2021-10- ... dable.html
by Weill Cornell Medical College
A team led by researchers at Weill Cornell Medicine, the New York Genome Center, Harvard Medical School, Massachusetts General Hospital and the Broad Institute of MIT and Harvard has profiled in unprecedented detail thousands of individual cells sampled from patients' brain tumors. The findings, along with the methods developed to obtain those findings, represent a significant advance in cancer research, and ultimately may lead to better ways of detecting, monitoring and treating cancers.
weatheriscool
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New 'almanac' may help clinicians better tailor cancer treatments
https://medicalxpress.com/news/2021-10- ... ments.html
by Allessandra Dicorato, Broad Institute of MIT and Harvard
Researchers have developed a tool that integrates a variety of molecular data from patients and tumors, with the goal of guiding precision medicine.

A promise of precision cancer medicine is for oncologists to tailor treatment based on a patient's unique molecular profile. In practice, however, interpreting the vast array of data points which make up a person and their cancer is challenging, and only made more difficult as oncologists begin to consider additional complex features. Databases and analytical tools that oncologists might use typically focus on individual alterations in the somatic, or uninherited, protein-coding regions of the genome; they generally do not include other important types of genetic data such as inherited variation or somatic fusions in genes. Scientists and oncologists also typically consider these features in isolation, rather than together or alongside traits that characterize a tumor globally.
weatheriscool
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Scientists Find a New Way To Reverse Immune Suppression in Cancer Tumors
TOPICS:CancerCell BiologyCornell UniversityLung CancerLungs
https://scitechdaily.com/scientists-fin ... er-tumors/
By Weill Cornell Medicine October 3, 2021
Immunofluorescent Lung Images Radiation Treatment

Malignant tumors can enhance their ability to survive and spread by suppressing antitumor immune cells in their vicinity, but a study led by researchers at Weill Cornell Medicine and NewYork-Presbyterian has uncovered a new way to counter this immunosuppressive effect.

In the study, published on September 20, 2021, in Nature Cancer, the researchers identified a set of anti-immunosuppressive factors that can be secreted by cells called club cells that line airways in the lungs. They showed in a mouse model of lung cancer that these club cell factors inhibit highly potent immunosuppressive cells called myeloid-derived suppressor cells (MDSCs), which tumors often recruit to help them evade antitumor immune responses.

The inhibition of the MDSCs led to an increase in the number of antitumor T cells at the tumor site, and greatly improved the effectiveness of FDA approved PD1 immunotherapy.

“These club cell-secreted factors are able to nullify immune suppressor cells that otherwise help tumors escape an effective antitumor response,” said co-senior author Dr. Vivek Mittal, director of research at the Neuberger Berman Lung Cancer Center and the Ford-Isom Research Professor of Cardiothoracic Surgery at Weill Cornell Medicine. “We’re excited by the possibility of developing these club cell factors into a cancer treatment.”
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Killer T cells could be recruited to ignite immune response against cancer

by Adrianna MacPherson, University of Alberta
https://medicalxpress.com/news/2021-10- ... ponse.html
A University of Alberta researcher has discovered how two signaling molecules recruit immune cells known as "killer" T cells to a specific type of colon cancer with more favorable patient outcomes. The finding may represent a therapeutic strategy to target other types of cancers.

Kristi Baker, assistant professor in the Department of Oncology, examined tumors from patients with mismatch repair deficient colorectal cancer, a type that affects about 10 to 15 per cent of patients. While 85 per cent of colorectal cancers come from polyps, the mismatch repair deficient subset is developed through a different set of mutations.

"All cancer cells have a lot of mutations, but this particular group has a significantly higher number—almost tenfold as much as some of the other cancers," said Baker, who is also a member of the Cancer Research Institute of Northern Alberta and the Women and Children's Health Research Institute.

That higher number of mutations is what gives patients with the mismatch repair deficient tumors more positive outcomes in general. The immune system can sometimes overlook tumors because they look so similar to normal cells, so they aren't recognized as something foreign that needs to be attacked. But the higher number of mutations in mismatch repair deficient tumors means they're very visible to the immune system.
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Small molecule therapeutic may prevent metastasis in colorectal cancer
https://medicalxpress.com/news/2021-10- ... ectal.html
by Rockefeller University
Colorectal cancer is projected to claim 53,000 lives in the United States this year alone, and as with most cancers, the disease is deadliest when it metastasizes. It follows that the most effective way to control it would be a drug that targets metastasis itself—preventing cancer cells from breaking off the primary tumor, or reining in rogue cells before they spread throughout the body and seed secondary tumors.

Now, a new study identifies a small molecule that could, in the future, be administered alongside standard chemotherapies to stave off colorectal cancer metastasis. The research, published in Science Advances, demonstrated how the compound, named RGX-202, foils a key pathway that cancer cells rely upon to hoard energy, thereby killing them and shrinking tumors in mice.

The findings have already led to a clinical trial in humans and may eventually give rise to a novel therapy that increases survival rates for multiple gastrointestinal cancers.

"Colorectal cancer is one of the top causes of cancer-related mortality," says Rockefeller's Sohail Tavazoie, head of the Elizabeth and Vincent Meyer Laboratory of Systems Cancer Biology. "We've found a critical pathway that promotes colorectal cancer metastasis and a novel therapeutic that appears to inhibit it."
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Team discovers novel strategy to tame aggressive breast cancer and starts clinical trial
https://medicalxpress.com/news/2021-10- ... ancer.html
by National Cancer Centre Singapore
A team of clinicians and scientists from the National Cancer Centre Singapore (NCCS), Singapore General Hospital (SGH) and A*STAR's Genome Institute of Singapore (GIS) has identified a novel method to treat triple-negative breast cancer (TNBC). They discovered that cancer cells switch between different cell states and are able to change from being less aggressive ("epithelial") to being more aggressive ("mesenchymal"), and vice versa. By converting highly aggressive cancer cells to become less aggressive, physicians can prime tumors to respond better to chemotherapy, which works to eliminate cancer cells. This discovery has led to the launch of a three-year long human clinical trial, BEXMET (Bexarotene-induced Mesenchymal-Epithelial Transition), to investigate this unconventional approach to treating TNBC.

TNBC is more aggressive than other breast cancer sub-types, with limited treatment options and a poor prognosis. TNBC tests negative for estrogen receptor (ER), progesterone receptor (PR) and human epithelial growth factor receptor-2 (HER2), hence the reference to 'triple-negative' in its name. This also means that treatments targeting ER, PR and HER2 are not effective. For that reason, chemotherapy is still the mainstay standard treatment for TNBC.

The development of novel oncology drugs is costly, and affordability and accessibility can be a challenge. The concept tested by the NCCS, SGH and GIS team involves altering cancer cell states so that they are more susceptible to currently available chemotherapy. This may be a cost-effective way to treat TNBC, with the potential to treat a wider range of other cancers.
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Study identifies sulfatase as potential drug target for inflammatory bowel disease and colorectal cancer
https://medicalxpress.com/news/2021-10- ... bowel.html
by University of Liverpool
A new study published in Nature has found that a single sulfatase contributes to the degradation of mucus that protects the intestinal lining, potentially leading to inflammatory bowel disease and colorectal cancer.

The human gut microbiota significantly impacts several aspects of intestinal health and disease, including inflammatory bowel disease (IBD) and colorectal cancer. In the colon, secreted mucus creates a barrier that separates gut microorganisms from the lining of the intestine, preventing close contact that can lead to these conditions.

Some gut bacteria are able to utilize mucin glycoproteins, the main mucus component, as a nutrient source. However, it remains unclear which bacterial enzymes initiate degradation of the complex O-glycans found in mucins.

Despite the critical roles of sulfatases in many biological processes, including diseases, the researchers from a group of Universities including the University of Liverpool, University of Gothenburg, and the University of Michigan aimed to address the significant knowledge gap regarding their specificity and mechanisms.

A major component of colonic mucus is mucin 2, a glycoprotein. Mucin glycosylation is variable along the gastrointestinal tract, with an increase in sulfation in the colon, especially in the distal colon.

To degrade the complex O-glycans found in mucins, some human gut bacteria
have evolved complex arsenals of degradative enzymes that include sulfatases.
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Gel enhances CAR-T immunotherapy benefits in brains surgically treated for glioblastoma
https://medicalxpress.com/news/2021-10- ... rains.html
by UNC Lineberger Comprehensive Cancer Center
Pairing a newly developed gel with immunotherapy that was delivered to post-surgical mouse brains with glioblastoma, a highly malignant and deadly cancer, improved the immunotherapy's effectiveness, report researchers from the University of North Carolina Lineberger Comprehensive Cancer Center and colleagues. The findings appeared Oct. 6, 2021, in Science Advances.

The researchers used CAR-T cell (chimeric antigen receptor-T cell) immunotherapy, which involves harvesting immune-system T cells from a patient and genetically re-engineering them in the lab to recognize targets on the surface of cancer cells. In this mouse study, the CAR-T cells and gel were placed to fill in the area where a glioblastoma tumor had just been surgically removed. Previous studies have shown that administering T cells alone has produced limited benefit.

Glioblastoma is an aggressive tumor that can form quickly in the brain and is diagnosed most often in people in their sixties. Only 40 percent of people live for one year after diagnosis; just 17 percent survive for two years. Surgery is the first treatment used but presents many challenges in removing the tumor while also allowing for wound healing.

"We developed a gel made of fibrin, a protein most often associated with helping blood to clot. Applying a gel substance to an area of the brain to aid CAR-T cell therapy is unique in glioblastoma treatment," said Edikan Ogunnaike, Ph.D., a biomedical engineer at UNC and first author of the article. "The gel aided CAR-T cell distribution in the brain by acclimating the T cells to the post-surgical wound environment while also stopping the tumor from recurring."
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Engineers report advance in rapid cancer detection and monitoring
https://medicalxpress.com/news/2021-10- ... ancer.html
by Laurie Fickman, University of Houston


When it comes to cancer detection, size matters. Traditional diagnostic imaging cannot detect tumors smaller than a certain size, causing missed opportunities for early detection and treatment. Circulating tumor exosomes are especially small cancer biomarkers and easy to miss. These nanovesicles are composed of molecules that reflect the parental cells. But, because they are tiny (~30-150nm in diameter) and complex, the precise detection of exosome-carried biomarkers with molecular specificity is elusive.

Until now, reports Wei-Chuan Shih, professor of electrical and computer engineering at the University of Houston Cullen College of Engineering, in IEEE Sensors journal.

"This work demonstrates, for the first time, that the strong synergy of arrayed radiative coupling and substrate undercut can enable high-performance biosensing in the visible light spectrum where high-quality, low-cost silicon detectors are readily available for point-of-care application," said Shih. "The result is a remarkable sensitivity improvement, with a refractive index sensitivity increase from 207 nm/RIU to 578 nm/RIU."
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