Senolytic Drugs Fail to Kill Cancerous Cells with Senescent Gene Expression Signatures, but a Gene Therapy Succeeds

Some cancerous cells express signatures normally associated with senescent cells, so why not try senolytic compounds against them? This is something of a full circle, given that most of the current senolytic drug candidates were originally characterized and tested as potential chemotherapeutics. The open access paper here is interesting for two points: firstly, that senolytic drugs didn't kill cancerous cells with a senescent signature, and secondly that a suicide gene therapy targeting that signature does work against both normal senescent cells and cancerous cells with a senescent signature. The gene therapy approach reported here is conceptually similar (at a very high level) to the Oisin Biotechnologies gene therapy used to destroy senescent cells, but less flexible. The Oisin Biotechnologies founders have shown that targeting p53, a cancer suppressor, rather than p16 / p16Ink4a, a signature of senescence, is highly effective against cancer, but it appears that p16 is also a viable trigger for cell killing gene therapy mechanisms in many cancers.

p16Ink4a arrests cell cycle progression by inhibiting the S phase. Cellular senescence, a tumor suppressive mechanism defined as irreversible growth arrest and induced by accumulation of DNA damage, is often associated to induction of p16Ink4a. Consequently, p16Ink4a is considered a strong tumor suppressor. Loss-of-function mutations affecting p16Ink4a are a common mark of various human tumors, and considered an essentia...

Source: Fight Aging! - March 7, 2018 Category: Research Authors: Reason Tags: Daily News Source Type: blogs