Therapeutics: MicroRNA-124 (miR-124)

Mouse studies suggest miR-124 could help treat castration-resistant prostate cancer (CRPC). In human prostate cancer cell lines, miR-124 plus Xtandi enzalutamide or Casodex bicalutamide decreased proliferation compared with either agent alone. In a human cell-based model of CRPC, miR-124 increased sensitivity to Xtandi compared with a scrambled miRNA. In a xenograft mouse model of androgen-dependent prostate cancer, intratumoral injection of miR-124 decreased tumor growth compared with a scrambled miRNA, and intratumoral injection of miR-124 plus oral Xtandi decreased tumor growth compared with either agent alone. Next steps could include testing in vivo whether long-term use of miR-124 prevents resistance to androgen receptor inhibitors.

Medivation Inc. and Astellas Pharma Inc. market Xtandi, an oral androgen receptor antagonist, to treat prostate cancer and have the compound in Phase III testing to treat breast cancer and Phase II testing to treat liver cancer...