Charting the multilevel molecular response to palbociclib in ER-positive breast cancer.

ABSTRACT: The addition of CDK4/6 inhibitors to endocrine therapy has significantly improved outcomes in HR+/HER2- breast cancer (BC). However, variable patient responses and acquired resistance remain a clinical challenge. We therefore defined the comprehensive molecular response to palbociclib, the most clinically used CDK4/6 inhibitor. Global analyses of gene expression, protein abundance, splicing, and chromatin accessibility revealed broad patterns and specific changes that result from CDK4/6-inhibition in BC cells. We uncovered unexpected feedback between CDK4/6 and estrogen-response signaling, which has clear clinical implications. We also revealed a widespread alternative splicing program that partially overlapped with genes whose expression is regulated, and which is expected to impact prote

SUBMITTER: Kavalipati A 

PROVIDER: S-EPMC12910112 | biostudies-literature | 2026 Mar

REPOSITORIES: biostudies-literature