Abstract
Prostate cancer (PCa) is a common cancer among American men and ranks second in terms of mortality in the United States. The current treatment modalities, castration, prostatectomy, radiation therapy, and androgen deprivation therapy (ADT) can only partially extend the life expectancy of the patients but eventually fail to completely cure the disease. Despite undergoing castration, patients still experience disease recurrence. This recurrence is led by the binding of the basal androgens present in blood plasma to the androgen receptor (AR). At this stage, the disease becomes castrate resistant prostate cancer (CRPC) showing resistance towards ADT, and there is no effective treatment available. In recent times, targeting energy metabolism pathways has gained immense interest as a potential therapeutic target. We envision that targeting the altered metabolism of PCa cells with a cisplatin prodrug, Platin-L, would disrupt the cancer cell's metabolism and sensitize them to cisplatin chemotherapy. The metabolically challenged cells would show a shift towards glucose oxidation, becoming vulnerable leading towards apoptosis. To delve deeper into understanding how Platin-L can be used to target the ADT resistant population we hypothesize whether inhibition of FAO by Platin-L may modulate AR activity and re-sensitize the ADT resistant cells. Androgens play a crucial role in fostering the growth, nourishment, and maintenance of PCa. Downregulation of FAO in castrate resistant PCa leads to changes in AR signaling pathway. Our study aims to investigate the downstream effects of the proteins involved in lipid metabolism which is controlled by AR signaling using both qualitative and quantitative analytic methods. To achieve our goals, we first verified whether Platin-L can target the cisplatin resistance in PCa and re-sensitize PCa towards cisplatin-based chemotherapy. Based on our preliminary studies in androgen-dependent and androgen-responsive PCa cell variants, we observe an effective therapeutic potential of Platin-L for re-sensitizing PCa towards ADT.