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Credit: The Wistar Institute PHILADELPHIA (April 1, 2021 Scientists at The Wistar Institute identified a new mechanism of transcriptional control of cellular senescence that drives the release of inflammatory molecules that influence tumor development through altering the surrounding microenvironment. The study, published in Nature Cell Biology, reports that methyltransferase-like 3 (METTL3) and 14 (METTL14) proteins moonlight as transcriptional regulators that allow for establishment of the senescence-associated secretory phenotype (SASP). Cellular senescence is a stable state of growth arrest in which cells stop dividing but remain viable and produce an array of inflammatory and growth-promoting molecules collectively defined as SASP. These molecules account for the complex crosstalk between senescent cells and neighboring cells and the effect of cellular senescence in various physiological processes and diseases. Although senescence is regarded as a potent bar ....
Scientists at the Wistar Institute reveal ARID1A mutations in ovarian clear cell carcinomas that typically do not respond to chemotherapy, result in an increased dependence on glutamine metabolism a vulnerability that can be therapeutically exploited. The authors showed that inhibiting glutamine metabolism with or without blocking immune checkpoints as well constitutes a viable therapeutic strategy. ....
Researchers Identify Link Between Ovarian Cancer, Metabolism by Angela Mohan on January 12, 2021 at 5:24 PM Nature Cancer. Up to 60% of ovarian clear cell carcinomas (OCCC) have inactivating mutations in the ARID1A tumor suppressor gene. These mutations are known genetic drivers of this type of cancer, which typically does not respond to chemotherapy and carries the worst prognosis among all subtypes of ovarian cancer. The laboratory of Rugang Zhang, Ph.D., deputy director of The Wistar Institute Cancer Center, professor and leader of the Immunology, Microenvironment & Metastasis Program, studies the effects of ARID1A inactivation to devise new mechanism-guided therapeutic strategies and combination approaches to enhance immunotherapy for ovarian cancer. ....
Link between driver of ovarian cancer, metabolism opens up new therapeutic strategies ANI | Updated: Jan 12, 2021 11:45 IST Washington [US], January 12 (ANI): Mutations that inactivate the ARID1A gene in ovarian cancer increase utilisation of the glutamine amino acid making cancer cells dependent on glutamine metabolism, according to a study by The Wistar Institute published online in Nature Cancer. Researchers also showed that pharmacologic inhibition of glutamine metabolism may represent an effective therapeutic strategy for ARID1A-mutant ovarian cancer. Up to 60 per cent of ovarian clear cell carcinomas (OCCC) have been inactivating mutations in the ARID1A tumor suppressor gene. These mutations are known genetic drivers of this type of cancer, which typically does not respond to chemotherapy and carries the worst prognosis among all subtypes of ovarian cancer. ....