Cancer News and Discussions

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Shrinking liver cancer tumors before transplant yields excellent outcomes, researchers report
https://medicalxpress.com/news/2022-07- ... ields.html
by The Mount Sinai Hospital
Treating liver cancer tumors to shrink them in order to allow the patient to qualify for a liver transplant leads to excellent 10-year post-transplant outcomes, according to new Mount Sinai research published in JAMA Surgery. The results validate current national policies around transplant eligibility.

Selection of patients with hepatocellular carcinoma (HCC), the most common form of liver cancer, for transplant has been guided for more than two decades by standards known as the Milan criteria. The Milan criteria state that transplantation should be performed in those with a single tumor of five centimeters or less in diameter or three tumors that are each three centimeters or less in diameter, have no macrovascular invasion, and no metastasis. Over time, the rising incidence of HCC and mortality rates in the United States have led to refinements to the selection policy, shifting the focus to guidelines that also incorporate tumor biology, response to bridging therapies, and waiting times for patients within and beyond the Milan criteria.

One aspect of the current criteria is known as downstaging: the process of applying liver directed therapy to tumors too big for the Milan criteria with the hope of reducing them to the suggested size. Downstaging is now an option in selecting suitable liver transplant candidates with initial tumors that exceed the criteria. However, liver cancer can recur after transplantation, either within the liver or outside of the liver. The treatment options of patients who have recurrence post transplantation is limited and prognosis is poor.
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Gene that causes deadliest brain tumor also causes childhood cancers, new research shows

by University of Virginia

A gene that University of Virginia (UVA) Health researchers have discovered is responsible for the deadliest type of brain tumor is also responsible for two forms of childhood cancer, the scientists have found.

The new discovery may open the door to the first targeted treatments for two types of rhabdomyosarcoma, a cancer of the soft tissue that primarily strikes young children.

The gene may also play an important role in other cancers that form in muscle, fat, nerves and other connective tissues in both children and adults, the research suggests.

"We accumulated multiple lines of evidence supporting [that the gene] AVIL is [a] powerful driver for both major types of rhabdomyosarcoma," said researcher Hui Li, Ph.D., of the University of Virginia School of Medicine's Department of Pathology and UVA Cancer Center. "The tumors are oncogene[s] addicted to AVIL, which supports the rationale to design therapeutic interventions to target AVIL in this childhood cancer."
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Chemotherapy drug temozolomide analog shows promise in treating glioma
https://medicalxpress.com/news/2022-07- ... lioma.html
by Bob Yirka , Medical Xpress

A team of researchers from Yale University and Yale School of Medicine has developed a temozolomide analog for use as a chemotherapy drug in treating glioma. In their paper published in the journal Science, the researchers describe the new drug and how it works to kill brain tumor cells. Roger Reddel and Adel Aref, with the University of Sydney's Children's Medical Research Institute, have published a Perspective piece in the same journal issue outlining the work done by the team in New Jersey

As the researchers note, glioblastoma (GBM) is the most common type of brain tumor in humans—it is also the most deadly. Just 5% of patients live five years beyond diagnosis. Treatment for patients with GBM involves radiation therapy and prescription of the chemotherapy drug temozolomide (TMZ). Such treatment is generally geared to prolonging life, not saving it. In this new effort, the researchers have developed a TMZ analog that has thus far proven to be more effective at killing GBM cells than standard TMZ.

TMZ works, Reddel and Aref, explain, by taking advantage of a GBM weakness—its cells are deficient in O6-methylguanine methyl transferase, (MGMT)—a protein that repairs DNA. Treatment with TMZ results in the development of DNA lesions that lead to cells self-destructing—the cancer cells die while the healthy brain cells survive by healing themselves. Unfortunately, patients tend to develop a resistance to the drug, which reduces its effectiveness until it is no longer useful. In this new effort, the researchers created a TMZ-like drug that also leads to DNA lesions and cells self-destructing but they made a change that prevents the tumor cells from developing a resistance to it.
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Reinvigorating 'lost cause' exhausted T cells could improve cancer immunotherapy
https://medicalxpress.com/news/2022-08- ... ancer.html
by University of Pittsburgh
During a battle with cancer, T cells can become exhausted and are no longer able to function properly. The early phase of exhaustion can sometimes be reversed with immunotherapy drugs, but once T cells become too exhausted, it had been thought that this state was irreversible. However, new insights from University of Pittsburgh and UPMC researchers suggest that even the most fatigued T cells can be revived.

In a study, published today in Science Immunology, the team profiled molecular features of T cells as they progressed from early to terminal exhaustion in a mouse model of melanoma. They unexpectedly found that even the most terminally exhausted T cells retain some capacity to be functional again and identified approaches to overcome exhaustion, opening potential new avenues for cancer immunotherapy.

"People think about terminally exhausted T cells as a lost cause, that there's no coming back from this state," said co-senior author Amanda Poholek, Ph.D., assistant professor of pediatrics and immunology at Pitt's School of Medicine and director of the Health Sciences Sequencing Core at UPMC Children's Hospital of Pittsburgh. "But given the right circumstances—the T cell version of rest—we show that they can come back. This finding could have incredible potential for immunotherapy."
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New AI technology integrates multiple data types to predict cancer outcomes
https://medicalxpress.com/news/2022-08- ... comes.html
by Brigham and Women's Hospital
While it's long been understood that predicting outcomes in patients with cancer requires considering many factors, such as patient history, genes and disease pathology, clinicians struggle with integrating this information to make decisions about patient care. A new study from researchers from the Mahmood Lab at Brigham and Women's Hospital reveals a proof-of-concept model that uses artificial intelligence (AI) to combine multiple types of data from different sources to predict patient outcomes for 14 different types of cancer. Results are published in Cancer Cell.

Experts depend on several sources of data, like genomic sequencing, pathology, and patient history, to diagnose and prognosticate different types of cancer. While existing technology enables them to use this information to predict outcomes, manually integrating data from different sources is challenging and experts often find themselves making subjective assessments.

"Experts analyze many pieces of evidence to predict how well a patient may do," said Faisal Mahmood, Ph.D., an assistant professor in the Division of Computational Pathology at the Brigham and associate member of the Cancer Program at the Broad Institute of Harvard and MIT. "These early examinations become the basis of making decisions about enrolling in a clinical trial or specific treatment regimens. But that means that this multimodal prediction happens at the level of the expert. We're trying to address the problem computationally."
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Researchers identify hormone from fat cells that restrains tumor growth in mice
https://medicalxpress.com/news/2022-08- ... tumor.html
by Emily Kagey, University of Michigan
A hormone secreted by fat cells can restrain the growth of liver tumors in mice, according to a new study from the University of Michigan Life Sciences Institute.

The findings offer a proof-of-concept for developing therapies against hepatocellular carcinoma, the most common form of liver cancer.

Jiandie Lin and his team use mice as a model to study how molecular and cellular changes are affected by nonalcoholic fatty liver disease, and how these changes consequently lead to the progression of this disease. While it begins as a relatively benign accumulation of fat in the liver, the disorder can develop into nonalcoholic steatohepatitis, or NASH, which increases the risk for liver cancer.

The liver contains scores of different cell types, including various immune cells. Using single-cell RNA sequencing, a technology for probing gene expression of individual cells within complex tissues, Lin and his team previously constructed a liver cell atlas and a blueprint of intercellular signaling in healthy and NASH mouse livers.
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Understanding why deadly brain cancer comes back
https://medicalxpress.com/news/2022-08- ... ancer.html
by University of Leeds
The deadliest form of brain cancer returns because tumors adapt to treatment by recruiting help from nearby healthy tissue, say researchers who are trying to find a cure for the disease.

A new study, by a global team including University of Leeds experts, has found that in response to treatment, high-grade gliomas appear to remodel the surrounding brain environment, potentially creating interactions with nearby neurons and immune cells in ways that protect the tumor cells and hide them from the body's defenses.

The team also found that lower grade tumors often develop a new mutation that allows the cells to start dividing more rapidly, potentially catapulting them into a higher-grade form.

Glioma brain tumors are rare, but a diagnosis is devastating because there is currently no cure. Low-grade gliomas have a better survival rate than, but often progress to high-grade gliomas. More than 90% of patients with high-grade tumors die within five years.
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Study offers insights into how pancreatic cancer develops
https://medicalxpress.com/news/2022-08- ... ancer.html
by Washington University School of Medicine
Pancreatic cancer has few treatment options and limited survival, with only 9% of patients still living five years after diagnosis.

But a detailed analysis of pancreatic cancer by researchers at Washington University School of Medicine in St. Louis has revealed details of two key transition points in the development of these tumors—the shift from normal cells to precancerous cells, and the change from precancerous to cancerous cells. Understanding these transitions will help lead to the development of novel therapies. The study also provides insights into treatment resistance and how immunotherapy could be harnessed to treat this aggressive tumor type.

The study, published Aug. 22 in the journal Nature Genetics, is part of the Human Tumor Atlas Network, funded by the National Cancer Institute's Cancer Moonshot program, all part of the National Institutes of Health (NIH).

Also, as part of an ongoing phase 1 immunotherapy clinical trial at Siteman Cancer Center—based at Barnes-Jewish Hospital and Washington University School of Medicine—the researchers are conducting the same detailed analyses performed in the current study to see how tumors from patients respond to two investigational drugs that prime the immune system to attack the cancer.
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Scientists discover surprise anticancer properties of common lab molecule
https://medicalxpress.com/news/2022-08- ... n-lab.html
by UNC Health

Scientists at the UNC School of Medicine have made the surprising discovery that a molecule called EdU, which is commonly used in laboratory experiments to label DNA, is in fact recognized by human cells as DNA damage, triggering a runaway process of DNA repair that is eventually fatal to affected cells, including cancer cells.

The discovery, published in the Proceedings of the National Academy of Sciences, points to the possibility of using EdU as the basis for a cancer treatment, given its toxicity and its selectivity for cells that divide fast.

"The unexpected properties of EdU suggest it would be worthwhile to conduct further studies of its potential, particularly against brain cancers," said study senior author Aziz Sancar, MD, Ph.D., the Sarah Graham Kenan Professor of Biochemistry and Biophysics at the UNC School of Medicine and member of the UNC Lineberger Comprehensive Cancer Center. "We want to stress that this is a basic but important scientific discovery. The scientific community has much work ahead to figure out if EdU could actually become a weapon against cancer."
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A gene not previously known to regulate immunity could turn tired T-cells around
https://medicalxpress.com/news/2022-08- ... cells.html
by University of California, San Francisco

T cells used in immunotherapy treatments can get exhausted by the task of fighting cancer cells or get shutdown as they enter tumors. Using a CRISPR-based edit on these cells' genomes, researchers at UC San Francisco and Gladstone Institutes have rendered the therapeutic cells more resilient. The discovery may help overcome a major factor limiting the success of these promising therapies in curbing both solid and liquid tumors.

"We've succeeded in engineering better, stronger, longer-lived T cells that we think will improve treatment of both blood and solid cancers," said Alex Marson, MD, Ph.D., who, along with cancer biologist Alan Ashworth, Ph.D., FRS led the study, published in Nature on Aug. 24, 2022. "It's an example of how we're using the power of CRISPR to accelerate the design of improved T-cell therapies."
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