Ma Lisi, Zong Xiangyun
Department of Breast Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China.
Front Oncol. 2020 Jan 24;10:5. doi: 10.3389/fonc.2020.00005. eCollection 2020.
Cellular metabolic reprogramming is now recognized as a hallmark of tumors. Altered tumor metabolism determines the malignant biological behaviors and phenotypes of cancer. More recently, studies have begun to reveal that cancer cells generally exhibit increased glycolysis or oxidative phosphorylation (OXPHOS) for Adenosine Triphosphate(ATP)generation, which is frequently associated with drug resistance. The metabolism of drug-resistant cells is regulated by the PI3K/AKT/mTOR pathway which ultimately confer cancer cells drug resistance phenotype. The key enzymes involved in glycolysis and the key molecules in relevant pathways have been used as targets to reverse drug resistance. In this review, we highlight our current understanding of the role of metabolic symbiosis in therapeutic resistance and discuss the ongoing effort to develop metabolic inhibitors as anti-cancer drugs to overcome drug resistance to classical chemotherapy.
细胞代谢重编程现已被公认为肿瘤的一个标志。肿瘤代谢改变决定了癌症的恶性生物学行为和表型。最近，研究开始揭示，癌细胞通常表现出糖酵解增加或通过氧化磷酸化（OXPHOS）来生成三磷酸腺苷（ATP），这常常与耐药性相关。耐药细胞的代谢受PI3K/AKT/mTOR通路调控，该通路最终赋予癌细胞耐药表型。糖酵解中涉及的关键酶以及相关通路中的关键分子已被用作逆转耐药性的靶点。在本综述中，我们着重阐述了目前对代谢共生在治疗耐药性中作用的理解，并讨论了正在进行的将代谢抑制剂开发为抗癌药物以克服对传统化疗耐药性的努力。
