Development of androgen-independent tumor cells and their implication for the treatment of prostatic cancer.

Development of androgen-independent prostatic cancer cells from androgen-responsive cells can occur by a variety of mechanisms (e.g., environmental adaptation, multifocal origin, or genetic instability). Regardless of the mechanism of development, however, once androgen-independent cancer cells become present within prostatic cancer, the tumor is no longer homogeneous but is now heterogeneous. Once a prostatic cancer is heterogeneously composed of both androgen-dependent and -independent cancer cells, androgen withdrawal therapy, no matter how complete, cannot be curative. In order to produce cures of such heterogeneous prostatic cancers, hormonal therapy must be combined simultaneously with chemotherapy early in the course of the disease so that all the cancer populations (i.e., androgen-dependent and -independent) can be simultaneously affected within an individual patient.