Pharmacological CDK4/6 inhibition reveals a p53-dependent senescent state with restricted toxicity

ABSTRACT: Cellular senescence is a state of stable growth arrest and a desired outcome of tumor suppressive interventions. Treatment with many anti-cancer drugs can cause premature senescence of non-malignant cells. These therapy-induced senescent cells can have pro-tumorigenic and pro-disease functions via activation of an inflammatory secretory phenotype (SASP). Inhibitors of cyclin-dependent kinases 4/6 (CDK4/6i) have recently proven to restrain tumor growth by activating a senescence-like program in cancer cells. However, the physiological consequence of exposing the whole organism to pharmacological CDK4/6i remains poorly characterized. Here, we show that exposure to CDK4/6i induces non-malignant cells to enter a premature state of senescence dependent on p53. We observe in mice and breast canc

SUBMITTER: Dr. Boshi Wang 

PROVIDER: S-SCDT-EMBOJ-2021-108946 | biostudies-other |

REPOSITORIES: biostudies-other