Macrophage Regulation of the Development of Castration-Resistant Prostate Cancer

Androgen deprivation therapy (ADT) is the front-line treatment for early and metastatic prostate cancer, and the development of tumor resistance to it has major clinical consequences. Cancer cells start to proliferate and tumors begin to regrow, requiring the administration of more generic anticancer treatments like surgery, radiotherapy, and/or chemotherapy. Tumor-associated macrophages are known to drive tumor resistance to a number of anti-cancer therapies. El-Kenawi and colleagues now demonstrate a novel mechanism underpinning their ability to do so in prostate tumors during ADT. This involves the accumulation of cholesterol by macrophages in tumors and its transfer to cancer cells, where it acts as a precursor for androgen biosynthesis and results in the activation of androgen receptors.See related article by El-Kenawi and colleagues, p. 5477.