Amity Institute of Molecular Medicine and Stem Cell Research, Amity University, Sector-125, Noida, Uttar Pradesh 201303, India.
Department of Microbiology, Kalyani University, West Bengal 741235, India.
Biochim Biophys Acta Rev Cancer. 2021 Aug;1876(1):188563. doi: 10.1016/j.bbcan.2021.188563. Epub 2021 May 7.
Epithelial ovarian cancer, the most lethal gynecological malignancy, is diagnosed at advanced stage, recurs and displays chemoresistance to standard chemotherapeutic regimen of taxane/platinum drugs. Despite development of recent therapeutic approaches including poly-ADP ribose polymerase inhibitors, this fatal disease is diagnosed at advanced stage and heralds strategies for early detection and improved treatment. Recent literature suggests that high propensity of ovarian cancer cells to consume and metabolize glucose via glycolysis even in the presence of oxygen (the 'Warburg effect') can significantly contribute to disease progression and chemoresistance and hence, it has been exploited as novel drug target. This review focuses on the molecular cues of aberrant glycolysis as drivers of chemo-resistance and aggressiveness of recurrent ovarian cancer. Furthermore, we discuss the status quo of small molecule inhibition of aerobic glycolysis and significance of metabolic coupling between cancer cells and tumor microenvironment as novel therapeutic interventions against this lethal pathology.
上皮性卵巢癌是最致命的妇科恶性肿瘤，通常在晚期被诊断出来，容易复发，并对紫杉醇/铂类药物的标准化疗方案产生耐药性。尽管最近开发了包括多聚 ADP 核糖聚合酶抑制剂在内的治疗方法，但这种致命疾病在晚期被诊断出来，需要寻找早期检测和改善治疗的策略。最近的文献表明，卵巢癌细胞即使在有氧气的情况下，通过糖酵解消耗和代谢葡萄糖的倾向（“Warburg 效应”），可能会显著促进疾病的进展和化疗耐药性，因此它已被作为新的药物靶点加以利用。这篇综述重点介绍了异常糖酵解的分子线索，这些线索是复发性卵巢癌化疗耐药性和侵袭性的驱动因素。此外，我们还讨论了有氧糖酵解的小分子抑制现状，以及癌细胞与肿瘤微环境之间代谢耦联的意义，作为针对这种致命病理的新的治疗干预措施。
