Vidal Raphael Silveira, Quarti Julia, Rodrigues Mariana Figueiredo, Rumjanek Franklin D, Rumjanek Vivian M
Instituto de Bioquímica Médica Leopoldo de Meis, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
Instituto de Nutrição Josué de Castro, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
Front Oncol. 2018 Apr 4;8:90. doi: 10.3389/fonc.2018.00090. eCollection 2018.
Cancer outcome has improved since introduction of target therapy. However, treatment success is still impaired by the same drug resistance mechanism of classical chemotherapy, known as multidrug resistance (MDR) phenotype. This phenotype promotes resistance to drugs with different structures and mechanism of action. Recent reports have shown that resistance acquisition is coupled to metabolic reprogramming. High-gene expression, increase of active transport, and conservation of redox status are one of the few examples that increase energy and substrate demands. It is not clear if the role of this metabolic shift in the MDR phenotype is related to its maintenance or to its induction. Apart from the nature of this relation, the metabolism may represent a new target to avoid or to block the mechanism that has been impairing treatment success. In this mini-review, we discuss the relation between metabolism and MDR resistance focusing on the multiple non-metabolic functions that enzymes of the glycolytic pathway are known to display, with emphasis with the diverse activities of glyceraldehyde-3-phosphate dehydrogenase.
自从引入靶向治疗以来，癌症治疗结果有所改善。然而，治疗成功仍然受到经典化疗相同的耐药机制（即多药耐药，MDR表型）的影响。这种表型会导致对具有不同结构和作用机制的药物产生耐药性。最近的报告表明，耐药性的获得与代谢重编程有关。高基因表达、主动转运增加和氧化还原状态的维持是少数几个增加能量和底物需求的例子。目前尚不清楚这种代谢转变在MDR表型中的作用是与其维持有关还是与其诱导有关。除了这种关系的本质之外，代谢可能代表了一个新的靶点，以避免或阻断一直影响治疗成功的机制。在这篇小型综述中，我们讨论代谢与MDR耐药性之间的关系，重点关注糖酵解途径的酶已知具有的多种非代谢功能，尤其强调3-磷酸甘油醛脱氢酶的多种活性。
