Therapeutics: Tumor necrosis factor receptor superfamily member 11a (RANK; TNFRSF11A; CD265); receptor activator of NF-κB ligand (RANKL; TNFSF11); breast cancer
Patient sample and mouse studies suggest inhibiting RANKL could help treat BRCA1-mutant breast cancer. In tissue samples from breast cancer patients, levels of the RANKL receptor RANK were higher in tumors and adjacent normal breast tissue from patients with BRCA1 mutations than in patients with BRCA2 mutations or wild-type BRCA1 and BRCA2. In breast tissue samples from BRCA1-mutant patients, RANKL was highly expressed in the tumor-adjacent normal tissue, and the anti-RANKL mAb Prolia denosumab decreased a marker of tumorigenicity compared with a control antibody. In a mouse model of spontaneous BRCA1-mutant breast cancer, a RANKL inhibitor tool compound or Prolia delayed disease onset compared with vehicle or a control antibody. Next steps include testing RANKL inhibitors in patient-derived BRCA1-mutant breast cancer cells and patient-derived xenograft animal models of BRCA1-mutant breast cancer.
Amgen Inc. and Daiichi Sankyo Co. Ltd. market Prolia for bone cancer and have the mAb approved for refractory hypercalcemia of malignancy (HCM) and in Phase III testing for rheumatoid arthritis and to delay or prevent bone metastases of breast cancer...