NF1-depleted ER⁺ breast cancers are differentially sensitive to CDK4/6 inhibitors.

ABSTRACT: Neurofibromin/NF1 is a RAS (rat sarcoma virus) GTPase-activating protein and estrogen receptor (ER) transcriptional corepressor. NF1^low status, identified by copy number loss or low mRNA/protein expression, is associated with endocrine therapy resistance in ~20% of ER⁺/HER2^- (human epidermal growth factor receptor 2) early-stage breast cancers. The identification of targeted treatments for NF1^low ER⁺/HER2^- breast cancer is therefore a priority. In this study, proteogenomic analysis of ER⁺/HER2^- breast cancer demonstrated that NF1^low tumors exhibited elevated cyclin-dependent kinase 4/6 (CDK4/6) activity. In cell lines, NF1 deletion had a dual effect on CDK4 activity: first, by promotin

SUBMITTER: Zheng ZY 

PROVIDER: S-EPMC12697068 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature