High p16 expression and heterozygous RB1 loss are biomarkers for CDK4/6 inhibitor resistance in ER⁺ breast cancer.

ABSTRACT: CDK4/6 inhibitors combined with endocrine therapy have demonstrated higher antitumor activity than endocrine therapy alone for the treatment of advanced estrogen receptor-positive breast cancer. Some of these tumors are de novo resistant to CDK4/6 inhibitors and others develop acquired resistance. Here, we show that p16 overexpression is associated with reduced antitumor activity of CDK4/6 inhibitors in patient-derived xenografts (n = 37) and estrogen receptor-positive breast cancer cell lines, as well as reduced response of early and advanced breast cancer patients to CDK4/6 inhibitors (n = 89). We also identified heterozygous RB1 loss as biomarker of acquired resistance and poor clinical outcome. Combination of the CDK4/6 inhibitor ribociclib with the PI3K inhibitor alpelisib showed anti

SUBMITTER: Palafox M 

PROVIDER: S-EPMC9452562 | biostudies-literature | 2022 Sep

REPOSITORIES: biostudies-literature