Mechanistic understanding of the role of ATRX in senescence provides new insight for combinatorial therapies with CDK4 inhibitors

Mol Cell Oncol. 2017 Nov 7;5(1):e1384882. doi: 10.1080/23723556.2017.1384882. eCollection 2018.


Senescence is an irreversible form of growth arrest and is generally considered a favorable outcome of cancer therapies, yet little is known about the molecular events that distinguish this state from readily reversible growth arrest (i.e. quiescence). Recently, we discovered that during therapy induced senescence the chromatin remodeling protein α-thalassemia, mental retardation, X-linked (ATRX) represses Harvey rat sarcoma viral oncogene homolog (HRAS), and repression of HRAS is necessary to establish senescence, suggesting how new clinical combinations might be used to achieve durable senescence.

Keywords: ATRX; CDK4 inhibitors; Therapy induced senescence; geroconversion.