Cancers Evade Immunotherapy by ‘Discarding the Evidence’ of Tumor-Specific Mutations


“Results of an initial study of tumors from patients with lung cancer or head and neck cancer suggest that the widespread acquired resistance to immunotherapy drugs known as checkpoint inhibitors may be due to the elimination of certain genetic mutations needed to enable the immune system to recognize and attack malignant cells. The study, conducted by researchers on the cells of five of their patients treated at the Johns Hopkins Kimmel Cancer Center, is described online Dec. 28 in Cancer Discovery.”

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Testosterone-Related Genetic Mutation Leads to Deadlier Outcomes In Prostate Cancer


“A team of Cleveland Clinic-Mayo Clinic researchers has shown for the first time that patients with advanced prostate cancer are more likely to die earlier from their disease if they carry a specific testosterone-related genetic abnormality.

“The findings, published in the September 2016 edition of The Lancet Oncology, suggest that a specific, inherited polymorphism, or inherited genetic change, in the HSD3B1 gene renders standard therapy for metastatic prostate cancer less effective. The researchers anticipate that the findings will lead to a simple blood test to detect the presence of the polymorphism, personalizing cancer treatment and indicating which patients may need more aggressive treatment.”

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Gene Mutation Signals Poor Prognosis for Pancreatic Tumors

“For patients with pancreatic neuroendocrine tumors, the presence of recently identified mutations in two key genes is a prognostic factor for poor outcome, researchers report.

” ‘We found loss of nuclear expression in about 23% of the tumors that we studied, and this loss of expression was associated with worse tumors from the outset,’ lead investigator Michelle Heayn, MD, a second-year pathology resident at the University of Pittsburgh Medical Center, told Medscape Medical News.

“Pancreatic tumors with neuroendocrine histology frequently respond to chemotherapy and have a more favorable prognosis than the more common pancreatic adenocarcinomas. However, the mutations are associated with worse disease-free and disease-specific survival.”

Tests for New Cancer Drugs Not Reliable Enough, Doctors Say

“Drugmakers including Bristol-Myers Squibb Co and Merck & Co are testing which patients will most benefit from new cancer treatments based on a protein found in their tumors, but that guide, known as a biomarker, may be too unreliable, researchers and health experts said.

“Bristol’s Opdivo and Merck’s Keytruda are both therapies designed to block a protein known as Programmed Death receptor (PD-1) that tumors use to evade the body’s natural defenses. Competitors Roche Holding, AstraZeneca and Pfizer also have similar drugs in an earlier stage of development. The drugmakers are conducting clinical trials that test patient tumors for a related protein called PD-L1.

“The new drugs are mainly aimed at patients with so-called solid tumors suffering from diseases including lung cancer and liver cancer. Lung cancer, the most common type, claims 1.8 million new cases each year worldwide. Sales of drugs to block PD-1 could reach $33 billion a year by 2022, according to Morningstar.”

Melanoma-Prone Families with CDKN2A Mutations Have Higher Rates of Additional Cancers

The gist: Some people whose families have high rates of melanoma may also have an increased risk of developing lung, pancreatic, and breast cancer. Specifically, people whose families have a mutation in the CDKN2A gene are more prone to developing other types of cancer. Oncologists can perform molecular testing to see whether a person has a CDKN2A mutation.

“Researchers discovered an increased prevalence of lung, pancreatic and breast cancer in families prone to melanoma who also carry CDKN2A germline mutations.

“In a cross-sectional study, researchers analyzed the effect of CDKN2A in 702 Spanish patients at high risk of developing melanoma and associations with clinical and family history features.

“Patients with sporadic multiple primary melanoma had a CDKN2A mutation prevalence of 8.5%, and those with familial melanoma had a CDKN2A mutation prevalence of 14.1%.

“The researchers found that the number of cases in the family, the number of primary melanomas and the age of onset were each associated with the presence of CDKN2A mutation.”

Predicting Prostate Cancer: Test Identifies New Methods for Treatment

“A genetic discovery out of the University of Pittsburgh School of Medicine is leading to a highly accurate test for aggressive prostate cancer and identifies new avenues for treatment.

“The analysis, published today in the American Journal of Pathology, found that prostate cancer patients who carry certain genetic mutations have a 91 percent chance of their cancer recurring. This research was funded by the National Institutes of Health (NIH), American Cancer Society and University of Pittsburgh Cancer Institute (UPCI).

” ‘Being able to say, with such certainty, that a patient is nearly guaranteed to see a recurrence of his prostate cancer means that doctors and patients can elect to be more aggressive in treating the cancer, knowing that the benefits likely outweigh the risks,’ said Jian-Hua Luo, M.D., Ph.D., professor of pathology, Pitt School of Medicine and member of UPCI. ‘Eventually, this could lead to a cure for prostate cancer through genetic therapy. With this discovery, we’re at the tip of the iceberg in terms of possibilities for improving patient outcomes.’ “

FGFR-Targeted Therapy Demonstrated Activity in Solid Tumors

“Patients with solid tumors with fibroblast growth receptor genetic alterations demonstrated tumor shrinkage with the novel agent BGJ398, according to study results presented at the American Association for Cancer Research Annual Meeting.

“The benefit was particularly apparent among patients with FGFR3-mutated urothelial cancer.

“ ‘An emerging concept in cancer treatment is to try to treat cancers with a genetically defined alteration with an inhibitor of the receptor tyrosine kinase that drives the cancer growth,’ Lecia V. Sequist, MD, MPH, associate professor of medicine at Harvard Medical School and Massachusetts General Hospital, said during a press conference. ‘This clinical study enrolled patients with many different tumor types. There are many types of tumors that have alterations of FGFR. Importantly, in contrast to other, more promiscuous multitargeted kinase inhibitors that happen to inhibit FGFR as one of their targets, BGJ398 has really no significant inhibition of the VEGF family of receptors.’ ”

Editor’s note: This clinical trial testing a new targeted therapy drug called BGJ398 found that it can shrink tumors that have mutations in the FGFR gene, as detected by molecular testing.

Aggressive Prostate Cancer Makes Use of Bad Cholesterol

For many years it has been known that cancer cells store and use fat molecules differently from the way normal cells do. Fat molecules, also called lipids, tend to accumulate in so-called lipid droplets within cells. These droplets can be seen under a microscope with special staining methods, but the precise mixture of the different kinds of lipids in an individual cell is difficult to analyze. Now, researchers have developed a new imaging technique called Raman spectromicroscopy, which allows for detailed analysis of lipids on a single-cell level. Continue reading…

On the Failure of Lung Cancer Drug Onartuzumab in a Phase III Clinical Trial

Most new cancer drugs fail clinical testing. Because they don’t make it to the pharmacy, we usually hear very little about them. But widespread media coverage made it hard to ignore the recent termination of a trial testing the drug onartuzumab. Details of the story raise concerns about the patient enrollment processes of some clinical trials. Continue reading…