Servante Juliette, Estranero Jasper, Meijer Lisethe, Layfield Rob, Grundy Richard
School of Life Sciences, University of Nottingham, Medical School, Nottingham, NG7 2UH, UK.
Children's Brain Tumor Research Centre, Medical School, Queen's Medical Centre, Nottingham, NG7 2UH, UK.
Oncotarget. 2018 Oct 16;9(81):35266-35277. doi: 10.18632/oncotarget.26186.
Brain tumors are the leading cause of cancer-related death in children and are the most challenging childhood cancer in relation to diagnosis, treatment, and outcome. One potential novel strategy to improve outcomes in cancer involves the manipulation of autophagy, a fundamental process in all cells. In cancer, autophagy can be thought of as having a "Janus"-like duality. On one face, especially in the early phases of cancer formation, autophagy can act as a cellular housekeeper to eliminate damaged organelles and recycle macromolecules, thus acting as tumor suppressor. On the other face, at later stages of tumor progression, autophagy can function as a pro-survival pathway in response to metabolic stresses such as nutrient depravation, hypoxia and indeed to chemotherapy itself, and can support cell growth by supplying much needed energy. In the context of chemotherapy, autophagy may, in some cases, mediate resistance to treatment. We present an overview of the relevance of autophagy in central nervous system tumors including how its chemical modulation can serve as a useful adjunct to chemotherapy, and use this knowledge to consider how targeting of autophagy may be relevant in pediatric brain tumors.
脑肿瘤是儿童癌症相关死亡的主要原因，并且在诊断、治疗和预后方面是最具挑战性的儿童癌症。一种改善癌症预后的潜在新策略涉及对自噬的调控，自噬是所有细胞中的一个基本过程。在癌症中，自噬可被认为具有一种类似“两面神”的双重性。一方面，特别是在癌症形成的早期阶段，自噬可充当细胞的“管家”，清除受损细胞器并回收大分子，从而起到肿瘤抑制作用。另一方面，在肿瘤进展的后期阶段，自噬可作为一种促生存途径，以应对诸如营养剥夺、缺氧等代谢应激，甚至对化疗本身作出反应，并可通过提供急需的能量来支持细胞生长。在化疗的背景下，自噬在某些情况下可能介导对治疗的抗性。我们概述了自噬在中枢神经系统肿瘤中的相关性，包括其化学调控如何可作为化疗的有用辅助手段，并利用这一知识来思考自噬靶向在儿童脑肿瘤中可能具有的相关性。
