Cellular growth factors as prospective therapeutic targets for combination therapy in androgen independent prostate cancer (AIPC).

Cancer is the second leading cause of death worldwide, with prostate cancer, the second most commonly diagnosed cancer among men. Prostate cancer develops in the peripheral zone of the prostate gland, and the initial progression largely depends on androgens, the male reproductive hormone that regulates the growth and development of the prostate gland and testis. The currently available treatments for androgen dependent prostate cancer are, however, effective for a limited period, where the patients show disease relapse, and develop androgen-independent prostate cancer (AIPC). Studies have shown various intricate cellular processes such as, deregulation in multiple biochemical and signaling pathways, intra-tumoral androgen synthesis; AR over-expression and mutations and AR activation via alternative growth pathways are involved in progression of AIPC. The currently approved treatment strategies target a single cellular protein or pathway, where the cells slowly develop resistance and adapt to proliferate via other cellular pathways over a period of time. Therefore, an increased research aims to understand the efficacy of combination therapy, which targets multiple interlinked pathways responsible for acquisition of resistance and survival. The combination therapy is also shown to enhance efficacy as well as reduce toxicity of the drugs. Thus, the present review focuses on the signaling pathways involved in the progression of AIPC, comprising a heterogeneous population of cells and the advantages of combination therapy. Several clinical and pre-clinical studies on a variety of combination treatments have shown beneficial outcomes, yet further research is needed to understand the potential of combination therapy and its diverse strategies.