Targeted Metabolic Alterations in Prostate Cancer: A Promising Therapeutic Strategy

The treatment of prostate cancer (PCa) remains a major challenge due to the development of resistance to androgen receptor (AR)-targeted therapies and paclitaxel-based chemotherapeutic agents, highlighting the need for novel therapeutic approaches. Unlike the majority of tumor cells that depend on aerobic glycolysis (the Warburg effect) for energy production, early stage PCa primarily utilizes oxidative phosphorylation (OXPHOS), while advanced-stage PCa shifts to aerobic glycolysis. Consequently, targeting metabolic alterations specific to PCa may represent a promising therapeutic strategy. This review initially delineates the glucose metabolism phenotype characteristic of healthy prostate cells as well as primary and metastatic PCa cells, which underpin the development and progression of the disease. Subsequently, it elaborates on the roles and mechanisms of inhibitors targeting key enzymes involved in glycolysis and the synthesis of OXPHOS in the context of PCa treatment. Finally, the review discusses inhibitors that concurrently target both glycolysis and OXPHOS, potentially mitigating the compensatory pathways that support cancer cell survival. Collectively, this review contributes to a deeper understanding of metabolic alterations in PCa and informs the ongoing development of therapeutic interventions.