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.

Automated summary

Androgen deprivation therapy (ADT) is a frontline treatment for early and metastatic prostate cancer, but tumor resistance to ADT can lead to major clinical consequences. Tumor-associated macrophages have been shown to drive tumor resistance to various anticancer therapies, and researchers have now identified a novel mechanism involving the transfer of cholesterol from macrophages to cancer cells during ADT, which activates androgen receptors and promotes tumor resistance.