Repurposing Metformin as Anticancer Drug: in Advanced Prostate Cancer

Advanced-stage PCa is usually treated with androgen-deprivation therapy (ADT). Most patients with metastatic disease who were managed with ADT eventually progress to castration-resistant prostate cancer (CRPC) and die of the disease. CRPC can be treated with docetaxel, abiraterone plus prednisone, enzalutamide, and cabazitaxel, which provide limited survival benefits. Thus, there is still a need to improve the therapeutic options available for advanced-stage prostate cancer patients. Targeting therapy-resistant cancer stem cells (CSCs )in prostate cancer provides a unique opportunity for novel therapeutic interventions. Metformin, a common well-tolerated oral biguanide prescribed for type II diabetes, could be used to sensitize prostate CSCs to current conventional anticancer therapies and improve the efficacy of treatment. Some studies reported that Metformin could enhance the effectiveness of ADT. Metformin augmented the antiproliferative and apoptotic effects of ADT in prostate cancer. The combination of these two drugs significantly reduces prostate cancer cell growth compared to monotherapy with either drug. Also, metformin might reduce the development of CRPC. Many studies showed that obesity and DM were linked to aggressive prostate cancer phenotype, including biochemical failure after radical prostatectomy and external beam radiotherapy with higher incidence of complications of ADT. Interestingly, metformin reduces the incidence of diabetes and the adverse metabolic effects of ADT, including hyperinsulinaemia and dyslipidaemia, and decreases myocardial infarction risk and prolongs survival in diabetic patients. To the best of our knowledge, after extensive computer research, there is no published results from prospective randomized trials evaluating role of metformin among men with high risk locally advanced or metastatic prostate cancer patients who will start treatment with ADT.