Mcl-1 Inhibitors as a Novel Class of Senolytic

Researchers working with prostate cancer cells here show that senescent cancer cells depend upon Mcl-1 to prevent programmed cell death, a novel target with existing drugs that may prove useful as general purpose senolytics, able to clear senescent cells from tissues. Cancers are highly varied, and this would have to be tested against the more usual types of senescent cell present in the aged body. Even if only applicable in the context of some cancers, however, this is still a useful discovery. Cancer survivors have a significantly reduced life expectancy in large part because they suffer a greatly increased burden of cellular senescence, and thus chronic inflammation, disruption of normal tissue function, and so forth. Efficient removal of those senescent cells would be beneficial. Cells subjected to treatment with anti-cancer therapies can evade apoptosis through cellular senescence. Persistent senescent tumor cells remain metabolically active, possess a secretory phenotype (SASP), and can promote tumor proliferation and metastatic dissemination. Removal of senescent tumor cells (senolytic therapy) has therefore emerged as a promising therapeutic strategy. Most of the currently available senotherapies for cancers are still restricted to Bcl-2 targeting. Here, we describe a population of senescent prostate cancer tumor cells that do not rely on Bcl-2 to survive. This population of cells upregulates Mcl-1 and after treatment with the Bcl-2 inhibitor Navitocla...
Source: Fight Aging! - Category: Research Authors: Tags: Daily News Source Type: blogs