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自噬功能障碍与癌细胞及其治疗意义相关。

Autophagy dysfunctions associated with cancer cells and their therapeutic implications.

机构信息

Molecular Biology, Medicine Faculty, Titu Maiorescu University, Bucharest, Romania.

Medicinal and Behavioral Sciences Faculty, Constantin Brâncuși University, Târgu - Jiu, Romania.

出版信息

Biomed Pharmacother. 2019 Jul;115:108892. doi: 10.1016/j.biopha.2019.108892. Epub 2019 Apr 25.

Abstract

Genomic analysis of human cancers indicates that the loss or mutation of core autophagy related genes, (ATG) is uncommon, whereas oncogenic events that activate autophagy and lysosomal biogenesis have been identified. Several studies have demonstrated that autophagy plays a wide variety of physiological and pathophysiological roles in cells: a cellular process that maintains the homeostasis of the normal cell, while self-defects can lead to a lawsuit to accelerate tumorigenesis and developing diseases, such as cancer. Depending on different contexts, autophagy dysfunctions may play a role: neutral, tumor-suppressive, or tumor-promoting. The process of autophagy may function in tumor suppression by mitigating metabolic stress and, in concert with apoptosis, by preventing tumor cell death by necrosis. In this case, optimal combination of autophagy inhibition (CQ, HCQ) with other conventional therapies - chemo or radiotherapy in a variety of tumor types in different phases can be successful approaches for improve the effect of anticancer therapies. This review examines recent insights of the molecular mechanism of autophagy and the potential roles of autophagy in cell death, cancer development, overview of the most recent therapeutic strategies involving autophagy modulators in cancer prevention and therapeutic opportunities.

摘要

人类癌症的基因组分析表明,核心自噬相关基因(ATG)的缺失或突变并不常见,而激活自噬和溶酶体发生的致癌事件已被确定。几项研究表明,自噬在细胞中发挥着广泛的生理和病理生理作用:这是一个维持正常细胞内稳态的细胞过程,而自身缺陷则可能导致加速肿瘤发生和发展疾病,如癌症。根据不同的情况,自噬功能障碍可能起作用:中性、肿瘤抑制或促进肿瘤。自噬过程可以通过减轻代谢应激,与细胞凋亡协同作用,防止肿瘤细胞坏死来抑制肿瘤,从而发挥肿瘤抑制作用。在这种情况下,自噬抑制(CQ、HCQ)与其他常规疗法(化疗或放疗)的最佳组合在不同阶段的多种肿瘤类型中可以成功地提高抗癌疗法的效果。本文综述了自噬的分子机制的最新研究进展,以及自噬在细胞死亡、癌症发展中的潜在作用,概述了涉及自噬调节剂的最新治疗策略在癌症预防和治疗中的机会。

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