Resumen
Prostate cancer is the second most common cancer in males. In prostate cancer cells, androgens bind and activate the intracellular mediator called Androgen Receptor that control cell proliferation and survival. Hormone deprivation therapy is administrated to reduce androgen levels and consequently tumour growth. Unfortunately, most patients develop resistance to hormone treatment over the years and novel hormonal agents, such as Abiraterone or Enzalutamide, are administered. However, many patients do not initially respond or become resistant to these drugs quickly. Firstly, we demonstrated that in hormonal sensitive human prostate cancer cells the combination therapy of Abiraterone plus Enzalutamide reduced cell growth and survival. Moreover, starting from these prostate cancer cell lines, we generated cellular models of resistance to hormonal deprivation alone or in combination with the novel hormonal agents. In all the cases, resistant cell lines restore Androgen Receptor expression, Androgen Receptor functionality, cell proliferation and migration in the absence of androgens. Importantly, these novel cellular models acquire cross-resistance to each other. These results are consistent with clinical trials in castration resistant prostate cancer patients and suggest the biological rationale to test the combination therapy of Abiraterone plus Enzalutamide as first-line treatment in hormone-sensitive prostate cancer patients before becoming hormonal resistant.