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Inhibiting autophagy to prevent drug resistance and improve anti-tumor therapy
Life Sciences ( IF 5.2 ) Pub Date : 2020-11-10 , DOI: 10.1016/j.lfs.2020.118745
Jofer Andree Zamame Ramirez , Graziela Gorete Romagnoli , Ramon Kaneno

Cytotoxic drugs remain the first-line option for cancer therapy but the development of drug-resistance by tumor cells represents a primary obstacle for successful chemotherapy. Autophagy is a physiological mechanism of cell survival efficiently used by tumor cells to avoid cell death and to induce drug-resistance. It is a macromolecular process, in which cells degrade and recycle intracellular substrates and damaged organelles to alleviate cell stress caused by nutritional deprivation, hypoxia, irradiation, and cytotoxic agents, as well. There is evidence that autophagy prevents cancer during the early steps of carcinogenesis, but once transformed, these cells show enhanced autophagy capacity and use it to survive, grow, and facilitate metastasis. Current basic studies and clinical trials show the feasibility of using pharmacological or molecular blockage of autophagy to improve the anticancer therapy efficiency. In this review, we overviewed the pathways and molecular aspects of autophagy, its role in carcinogenesis, and the evidence for its role in cancer adaptation and drug-resistance. Finally, we reviewed the clinical findings on how the autophagy interference helps to improve conventional anticancer therapy.



中文翻译:

抑制自噬以预防耐药性并改善抗肿瘤治疗

细胞毒性药物仍然是癌症治疗的一线选择,但是肿瘤细胞对药物的耐药性发展是成功化疗的主要障碍。自噬是肿瘤细胞有效利用的细胞存活的生理机制,以避免细胞死亡并诱导耐药性。这是一个大分子过程,其中细胞降解并循环利用细胞内底物和受损的细胞器,以减轻由营养缺乏,缺氧,辐射和细胞毒性剂引起的细胞应激。有证据表明自噬可在癌变的早期阶段预防癌症,但是一旦转化,这些细胞将显示出增强的自噬能力,并将其用于生存,生长和促进转移。当前的基础研究和临床试验表明,使用自噬的药理学或分子阻断来提高抗癌治疗效率的可行性。在这篇评论中我们概述了自噬的途径和分子方面,其在致癌作用中的作用,以及其在癌症适应和耐药性中作用的证据。最后,我们回顾了自噬干扰如何帮助改善常规抗癌治疗的临床发现。

更新日期:2020-11-12
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