Andrògen – Independència en el cáncer de próstata

Abstract

Prostate cancer is currently one of the leading causes of death in men. The number of affected people is increasing, and future forecasts for them are not comforting. This is due to a number of cases where, despite the aggressive treatment against it, they lead to a type of castration-resistant prostate cancer (CRPC) which is now lethal. At the moment the treatment for prostate cancer is based on surgery or radiation, with or without androgen deprivation therapy (ADT), whereas in cases where the cancer has already progressed and spread, treatment includes radiation together with ADT or systemic treatments, which contain chemotherapy. Progression to CRPC occurs after ADT. Androgen ablation is the principal therapy for progressive prostate cancer, causing regression of tumors that are dependent on androgens. Cancers that are not healed by the surgery can end up becoming tumors independent of androgens, which makes anti-androgen therapy an ineffective therapy for these cases. It targets the androgen receptor (AR) and inhibits the proliferation and survival pathways induced by it. It has been shown that AR reactivation develops in CRPC despite ADT therapy. Similarly, the presence of cell populations independent of AR in CRPC has also been identified. While AR signalling has been proposed as the main axis leading to CRPC, independent AR signalling pathways may also present additional mechanisms leading to progression to CRPC. Therefore, in order to understand how to reach the CRPC stage and when androgen independence is achieved, an understanding of the metabolic and molecular pathways of androgens will be required. In addition, these mechanisms can occur simultaneously and distinctly in each patient, making it more difficult to decide which treatment to use. A number of therapeutic agents to inhibit these pathways have been approved by the FDA, but unfortunately resistance has also been developed against them. Due to the multiple pathways that cancer has to avoid treatments, another focus of study is the best strategy to integrate therapeutic agents and the most optimal sequencing of these in each case to be able to anticipate and overcome any mechanism that the cancer may use