After skin cancer, prostate cancer is the most common cancer in U.S. men and the second-most deadly cancer for men. Androgen deprivation is the standard of treatment for patients with advanced-stage disease. However, the response to androgen suppression is not durable, and eventually men with metastatic disease will transition to castration-resistant prostate cancer.
Researchers in the United Kingdom are looking at a new class of drugs that attacks cancer indirectly through a network of signals, which may prevent or overcome such drug resistance. The findings of the study were published in Cancer Research.
The study, which was conducted in mouse models, found that drugs called Hsp90 inihibitors destabilize proteins that prostate cancer cells use to evade existing treatments. The researchers call the treatments “network drugs” because they target a network of signals, not just one pathway the way most current treatments do. This type of activity is less likely to result in drug resistance.
Among the many ways Hsp90 inhibitors are effective are in the reduction of levels of normal androgen receptors and AKT and GR, which are two molecules necessary for prostate cancer growth. They also appear to block production of abnormal versions of androgen receptors, specifically AR-V7, the most common androgen receptor variant. Cancer cells use abnormal androgen receptors to evade standard treatments that target only healthy androgen receptors. Hsp90 worked in a novel way to interfere with messenger RNA and reduce AR-V7 production.
Additional studies are being conducted to verify the findings and also determine Hsp90’s effectiveness for other types of cancer.