Glycolytic Enzyme Enolase-1 (ENO-1) as a Novel Target for Neuroendocrine-Like Prostate Cancer: A Review of Up-to-date Research and Future Prospects
Prostate Cancer (PCa) remains a significant health burden, with advanced cases presenting significant challenges for treatment. Taxane-based chemotherapy has been the last line of defense for men with advanced PCa, but chemoresistance often leads to treatment failure. Targeted therapy using the Protein-Specific Membrane Antigen (PSMA) has shown promise; however, neuroendocrine-like PCa (NEPC) poses a hurdle due to its limited response to PSMA-RLT, attributed to the absence of PSMA expression. This review explores a promising alternative target, the glycolytic enzyme enolase-1 (ENO-1), which displays differential expression patterns in African American (AA) and European American (EA) men with PCa and could potentially serve as a novel therapeutic target for NEPC. Neuroendocrine-Like Prostate Cancer (NEPC) is a rare and aggressive subtype of prostate cancer, accounting for less than 1% of all cases, but its incidence has been reported to be increasing. NEPC is characterized by the loss of androgen receptor signaling and activation of neuroendocrine pathways, contributing to an adverse clinical outcome. Patients diagnosed with NEPC have a higher chance of metastasis and lower overall survival rates compared to those diagnosed with conventional prostate cancer. Furthermore, NEPC is more commonly diagnosed in African American patients, indicating potential ethnic disparities.
Despite recent progress in understanding the genomic and molecular basis of NEPC, there is still no standard treatment for this aggressive form of prostate cancer. Chemotherapy, radiation therapy, and androgen deprivation therapy are commonly used but with limited effectiveness. Therefore, more research is needed to better understand the underlying mechanisms of NEPC, discover new therapeutic targets, and develop more effective treatments.
The identification of alternative therapeutic targets, such as ENO-1, offers a promising avenue for addressing the challenges posed by NEPC. ENO-1's differential expression patterns in AA and EA men with PCa present an opportunity to personalize treatment approaches and address potential ethnic disparities in NEPC incidence. However, further research is essential to validate ENO-1's efficacy as a targeted therapy for NEPC and to develop novel treatment strategies to improve clinical outcomes for patients with this aggressive prostate cancer subtype. The review emphasizes the urgent need for ongoing research efforts in this area to pave the way for more effective and personalized treatments for NEPC patients.
