Targeting Androgen Regulators to Fight Therapy Resistant Prostate Cancer
Prostate cancer cells rely on androgen, mainly testosterone and its metabolites dehydrotestosterone, to maintain growth. Surgical or chemical castration to deprive testosterone in the blood is one of the commonly used treatments for high-risk prostate cancer. Generally, patients respond well to the treatment initially. However, almost all patients inevitably experience recurrence of the disease that is no longer sensitive to castration.
This recurrent prostate cancer is called castration resistant, or castration recurrent prostate cancer. Castration resistant prostate cancer is incurable and the most life-threatening form of the disease. How prostate cancer progresses to castration resistant prostate cancer remains elusive.
By comparing a panel of prostate cancer cell lines derived from castration-sensitive and castration-resistant prostate cancer, Dr. Li Tang found that castration-resistant prostate cancer cells are able to maintain testosterone at high level in cells by regulating expression of androgen transporters and inactivating enzymes. It has been known that castration does not completely eliminate testosterone in the blood. The residual amount of testosterone after castration may be sufficient to sustain prostate cancer cell growth if they could be taken up efficiently and maintained at an optimal level. Therefore, alteration of androgen transporters and inactivating enzymes may play a critical role in the development of castration resistant prostate cancer.
This project funded by Roswell Park Alliance Foundation will examine the expression profiles of androgen regulators in clinical tissue samples of castration-sensitive and castration-resistant prostate cancer, and to characterize the efficiency of these regulators in uptake and maintenance of androgen.
The study is the first step of an endeavor to define a new mechanism of prostate cancer progression to castration resistant disease, and more importantly, may lead to identification of a new class of therapeutic targets and to discover a new panel of markers for predicting the possibility of development of castration resistant prostate cancer.
The study's long-term goal is geared toward reducing the mortality from castration resistant prostate cancer, which has not been improved by current modalities of treatment.