Departments of Pharmacology and Toxicology and Medicine and Massey Cancer Center; Virginia Commonwealth University; Massey Cancer Center; Richmond, VA USA.
Autophagy. 2013 Sep;9(9):1263-5. doi: 10.4161/auto.25233. Epub 2013 Jun 12.
Two primary forms of autophagy have been identified in the field of cancer therapy based on their apparent functions in the tumor cell; these are the cytoprotective form that could, in theory, be inhibited for the purpose of sensitization to radiation and chemotherapeutic drugs and the "cytotoxic" form that either mediates or contributes to the actions of these treatment modalities. Surprisingly, to date, no clear-cut biochemical or molecular characteristics have been identified that might serve to distinguish between these two forms. In this commentary, we develop the concept of an additional form of autophagy that is nonprotective in that its inhibition neither sensitizes the tumor cell to exogenous stress (again, chemotherapy or radiation) nor protects the cell from the impact of these treatments. This form of autophagy also fails to exhibit any characteristics that might distinguish it from the cytoprotective and/or cytotoxic forms of autophagy. However, the existence of nonprotective autophagy is of potential significance in that it contributes to the challenge of predicting when the strategy of autophagy suppression might prove to have therapeutic benefit in the clinical treatment of cancer.
基于其在肿瘤细胞中的明显功能，癌症治疗领域已经确定了两种主要的自噬形式；这些是细胞保护形式，可以理论上被抑制以增加对辐射和化疗药物的敏感性，以及“细胞毒性”形式，它介导或有助于这些治疗方式的作用。令人惊讶的是，迄今为止，尚未确定明确的生化或分子特征，可以用于区分这两种形式。在这篇评论中，我们提出了另一种自噬形式的概念，这种自噬是非保护性的，因为其抑制既不会使肿瘤细胞对外源应激（再次是化疗或辐射）敏感，也不会保护细胞免受这些治疗的影响。这种自噬形式也没有表现出任何可以将其与细胞保护和/或细胞毒性自噬形式区分开来的特征。然而，非保护性自噬的存在具有潜在意义，因为它增加了预测自噬抑制策略何时可能在癌症的临床治疗中具有治疗益处的挑战。
