RANK is a poor prognosis marker and a therapeutic target in ER-negative postmenopausal breast cancer.

ABSTRACT: Despite strong preclinical data, the therapeutic benefit of the RANKL inhibitor, denosumab, in breast cancer patients, beyond the bone, is unclear. Aiming to select patients who may benefit from denosumab, we hereby analyzed RANK and RANKL protein expression in more than 2,000 breast tumors (777 estrogen receptor-negative, ER^- ) from four independent cohorts. RANK protein expression was more frequent in ER^- tumors, where it associated with poor outcome and poor response to chemotherapy. In ER^- breast cancer patient-derived orthoxenografts (PDXs), RANKL inhibition reduced tumor cell proliferation and stemness, regulated tumor immunity and metabolism, and improved response to chemotherapy. Intriguingly, tumor RANK protein expression associated with poor progn

SUBMITTER: Ciscar M 

PROVIDER: S-EPMC10086586 | biostudies-literature | 2023 Apr

REPOSITORIES: biostudies-literature