Sharma Khushboo, Goehe Rachel, Beckta Jason M, Valerie Kristoffer, Gewirtz David A
Virginia Commonwealth University, Departments of Pharmacology and Toxicology.
Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, MD, 20892.
EXCLI J. 2014 Feb 25;13:178-91. eCollection 2014.
Autophagy is a natural self-degradative process by which cells eliminate misfolded proteins and damaged organelles. Autophagy has been shown to have multiple functions in tumor cells that may be dependent on the tumor type and the treatment conditions. Autophagy can have a cytoprotective role and be thought of as a survival mechanism or be cytotoxic in nature and mediate cell death. Radiation, one of the primary treatments for many different types of cancer, almost uniformly promotes autophagy in tumor cells. While autophagy produced in response to radiation is often considered to be cytoprotective, radiation-induced autophagy has also been shown to mediate susceptibility to radiation. This review addresses the complexity of autophagy in response to radiation treatment in three different cancer models, specifically lung cancer, breast cancer and glioblastoma. A deeper understanding of the different roles played by autophagy in response to radiation should facilitate the development of approaches for enhancing the therapeutic utility of radiation by providing strategies for combination treatment with unique radiosensitizers as well as preventing the initiation of strategies which are likely to attenuate the effectiveness of radiation therapy.
自噬是一种天然的自我降解过程，通过该过程细胞可清除错误折叠的蛋白质和受损的细胞器。自噬在肿瘤细胞中具有多种功能，这可能取决于肿瘤类型和治疗条件。自噬可以发挥细胞保护作用，被视为一种生存机制，或者本质上具有细胞毒性并介导细胞死亡。放射治疗是许多不同类型癌症的主要治疗方法之一，几乎一致地会促进肿瘤细胞中的自噬。虽然因辐射产生的自噬通常被认为具有细胞保护作用，但辐射诱导的自噬也已被证明可介导对辐射的敏感性。本综述探讨了在三种不同癌症模型（即肺癌、乳腺癌和胶质母细胞瘤）中自噬对放射治疗反应的复杂性。更深入地了解自噬在对辐射反应中所起的不同作用，应有助于通过提供与独特放射增敏剂联合治疗的策略以及防止可能削弱放射治疗效果的策略的启动，来开发增强放射治疗效用的方法。
