Oncogene induced senescence and senescence-associated secretory phenotype (SASP) determines the efficacy of palbociclib in PIK3CA mutated colorectal cancer

Palbociclib, a classic CDK4/6 inhibitor, has been extensively studied in the context of targeted cancer therapy. We have systematically investigated the applicability of palbociclib in colorectal cancer, utilizing high-throughput sequencing and other methods to explore its resistance mechanisms. Our findings reveal that PIK3CA gene mutations promote a palbociclib-induced senescent phenotype and alter the expression profile of SASP factors. Among these, the SASP factor LCN2 contributes to cellular tolerance to palbociclib by upregulating EGFR protein expression. In summary, our sequencing data provide a molecular framework for the relationship between PIK3CA gene mutations and both palbociclib-induced cellular senescence and resistance.