Evaluation of Androgen Receptor Function in Prostate Cancer Prognosis and Therapeutic Stratification

Prostate cancer is the most common non-skin cancer and the third leading cause of cancer mortality in American men. While prostate cancer is detected early, it remains a challenge to distinguish between aggressive and indolent forms of the disease, and to make the best therapy choice for individual patients at early stages of the disease.

It is a widely accepted concept that gaining knowledge about the status of cancer in individual patients through defining molecular signatures may complement and improve current traditional prognosis and therapy decisions. In prostate cancer, prognostic and therapeutic molecular markers are currently not entered the general clinical practice. This proposal, based on the unique resources and ongoing translational research endeavors of the Center for Prostate Diseases where we have developed a functionally relevant panel of genes for prostate cancer prognosis and therapeutic stratification.

Initially, prostate cancer development is driven by the male hormone androgen through the androgen receptor. However, in some patients androgen receptor becomes dysfunctional at late stages of tumorigenesis. These patients are more likely to die from prostate cancer through generally incurable metastasis. Early knowledge of the androgen receptor dysfunctions -- what would make prostate tumors refractory to routine androgen ablation therapy -- should help in patient stratification for other emerging therapeutic strategies.

We propose here a novel approach developed in our laboratory to evaluate patients at the early stage of prostate cancer for potential dysfunctions of the androgen receptor by measuring the expression of a functionally relevant panel of genes for the accurate monitoring of androgen receptor function. This approach is direct and can be easily addressed from human prostate cancer tissues (surgery or diagnostic biopsy specimens) at early stages of the disease. This concept provides a quantitative measure able to differentiate androgen receptor function from dysfunction that when combined with other traditional disease characteristics as part of a nomogram can improve prognostic accuracy and can be used for the therapeutic stratification and monitoring of treatment efficacy in prostate cancer patients.