Barbeau Lydie M O, Keulers Tom G H, Rouschop Kasper M A
Department of Radiation Oncology (Maastro), GROW School for Oncology and Developmental Biology, Maastricht University Medical Centre+, 6200MD Maastricht, The Netherlands.
Cancers (Basel). 2020 Aug 31;12(9):2463. doi: 10.3390/cancers12092463.
Recent advances in cancer treatment modalities reveal the limitations of the prevalent "one-size-fits-all" therapies and emphasize the necessity to develop personalized approaches. In this perspective, identification of predictive biomarkers and intrinsic vulnerabilities are an important advancement for further therapeutic strategies. Autophagy is an important lysosomal degradation and recycling pathway that provides energy and macromolecular precursors to maintain cellular homeostasis. Although all cells require autophagy, several genetic and/or cellular changes elevate the dependence of cancer cells on autophagy for their survival and indicates that autophagy inhibition in these tumors could provide a favorable addition to current therapies. In this context, we review the current literature on tumor (sub)types with elevated dependence on autophagy for their survival and highlight an exploitable vulnerability. We provide an inventory of microenvironmental factors, genetic alterations and therapies that may be exploited with autophagy-targeted approaches to improve efficacy of conventional anti-tumor therapies.
癌症治疗方式的最新进展揭示了普遍存在的“一刀切”疗法的局限性，并强调了开发个性化方法的必要性。从这个角度来看，识别预测性生物标志物和内在脆弱性是进一步治疗策略的重要进展。自噬是一种重要的溶酶体降解和循环途径，它提供能量和大分子前体以维持细胞稳态。虽然所有细胞都需要自噬，但一些基因和/或细胞变化提高了癌细胞对自噬的生存依赖性，这表明在这些肿瘤中抑制自噬可以为当前疗法提供有益补充。在此背景下，我们回顾了当前关于对自噬生存依赖性增加的肿瘤（亚）类型的文献，并突出了一个可利用的脆弱性。我们提供了一份微环境因素、基因改变和疗法的清单，这些因素和疗法可通过自噬靶向方法加以利用，以提高传统抗肿瘤疗法的疗效。
