Abstract GS3-06: Rb Functions as a Transcriptional Activator of ER Targets Following CDK4/6 Inhibition in Luminal Breast Cancer

AC Watt; A Ahn; C Blyth; J Dixon-Douglas; K Ambani; R Coulson; M Taylor; K Chan; C Dietrich; BE Russ; S Ramm; CA Mahendra; K Lu; N Pires; E Lim; S Chandarlapaty; F Andre; S Goel

Journal article

Abstract GS3-06: Rb Functions as a Transcriptional Activator of ER Targets Following CDK4/6 Inhibition in Luminal Breast Cancer

AC Watt, A Ahn, C Blyth, J Dixon-Douglas, K Ambani, R Coulson, M Taylor, K Chan, C Dietrich, BE Russ, S Ramm, CA Mahendra, K Lu, N Pires, E Lim, S Chandarlapaty, F Andre, S Goel

Clinical Cancer Research | American Association for Cancer Research (AACR) | Published : 2026

DOI: 10.1158/1557-3265.sabcs25-gs3-06

Abstract

Abstract CDK4/6 inhibitors induce durable responses in estrogen receptor-positive (ER+) breast cancer, primarily via activation of the tumor suppressor Rb. While Rb is classically viewed as a repressor of E2F-dependent cell cycle genes, evidence from the pre-genomic era suggested broader roles in gene regulation. Here, we identify a previously unrecognized function of Rb as a transcriptional activator in luminal breast cancer, with key implications for endocrine sensitivity and resistance. Using CUT&RUN, we mapped genome-wide Rb binding in ER+ breast cancer cell lines (MCF7, ZR-75-1) and a patient-derived xenogra..

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