Cellular senescence in the response of HR⁺ breast cancer to radiotherapy and CDK4/6 inhibitors.

ABSTRACT:

Background

Preclinical evidence from us and others demonstrates that the anticancer effects of cyclin-dependent kinase 4/6 (CDK4/6) inhibitors can be enhanced with focal radiation therapy (RT), but only when RT is delivered prior to (rather than after) CDK4/6 inhibition. Depending on tumor model, cellular senescence (an irreversible proliferative arrest that is associated with the secretion of numerous bioactive factors) has been attributed beneficial or detrimental effects on response to treatment. As both RT and CDK4/6 inhibitors elicit cellular senescence, we hypothesized that a differential accumulation of senescent cells in the tumor microenvironment could explain such an observation, i.e., the inferiority of CDK4/6 inhibition with palbociclib (P) followed by RT (P→RT) as comp

SUBMITTER: Klapp V 

PROVIDER: S-EPMC9921325 | biostudies-literature | 2023 Feb

REPOSITORIES: biostudies-literature