Desbats Maria Andrea, Giacomini Isabella, Prayer-Galetti Tommaso, Montopoli Monica
Department of Medicine, University of Padova, Padova, Italy.
Veneto Institute of Molecular Medicine, Padova, Italy.
Front Oncol. 2020 Mar 6;10:281. doi: 10.3389/fonc.2020.00281. eCollection 2020.
Resistance of cancer cells to chemotherapy is the first cause of cancer-associated death. Thus, new strategies to deal with the evasion of drug response and to improve clinical outcomes are needed. Genetic and epigenetic mechanisms associated with uncontrolled cell growth result in metabolism reprogramming. Cancer cells enhance anabolic pathways and acquire the ability to use different carbon sources besides glucose. An oxygen and nutrient-poor tumor microenvironment determines metabolic interactions among normal cells, cancer cells and the immune system giving rise to metabolically heterogeneous tumors which will partially respond to metabolic therapy. Here we go into the best-known cancer metabolic profiles and discuss several studies that reported tumors sensitization to chemotherapy by modulating metabolic pathways. Uncovering metabolic dependencies across different chemotherapy treatments could help to rationalize the use of metabolic modulators to overcome therapy resistance.
癌细胞对化疗的耐药性是癌症相关死亡的首要原因。因此，需要新的策略来应对药物反应的逃避并改善临床结果。与细胞生长失控相关的遗传和表观遗传机制导致代谢重编程。癌细胞增强合成代谢途径，并获得除葡萄糖外使用不同碳源的能力。缺氧和营养匮乏的肿瘤微环境决定了正常细胞、癌细胞和免疫系统之间的代谢相互作用，从而产生代谢异质性肿瘤，这些肿瘤将对代谢疗法产生部分反应。在这里，我们深入探讨最著名的癌症代谢特征，并讨论几项报告通过调节代谢途径使肿瘤对化疗敏感的研究。揭示不同化疗治疗中的代谢依赖性有助于合理使用代谢调节剂来克服治疗耐药性。
