Mechanisms of androgen-independent tumor growth

In the setting of advanced prostatic carcinoma, castration results in a high initial response rate. Unfortunately, the benefit of such therapy is usually temporary owing to the fact that surviving tumor cells generally progress to an untreatable androgen-independent condition. Progression to androgen independence is a complex process. Several hypotheses for the mechanism of androgen independence exist, including clonal selection, tumor adaptation, and the activation of previously androgen-repressed genes that substitute for androgens in maintaining the viability of tumor-causing stem cells. In this article we will discuss the theoretical concepts underlying androgen independence as well as the concepts of androgen dependence, stepwise malignant transformation, and upregulation of constitutive growth factors.