To live or let die: Unclear task of autophagy in the radiosensitization battle

• Published in: Radiotherapy and oncology 2016-05, Vol.119 (2), p.265-275
• Main Authors: Ondrej, Martin, Cechakova, Lucie, Durisova, Kamila, Pejchal, Jaroslav, Tichy, Ales
• Format: Article
• Language: English
• Subjects: Ataxia Telangiectasia Mutated Proteins - physiology; Autophagy; Autophagy - radiation effects; Cell Hypoxia; Chloroquine - pharmacology; Hematology, Oncology and Palliative Medicine; Humans; Induction; Inhibition; Ionizing radiation; Membrane Proteins - physiology; Neoplasms - radiotherapy; Phosphatidylinositol 3-Kinases - physiology; Proto-Oncogene Proteins - physiology; Radiation Tolerance; Radiosensitization; Radiotherapy
• ISSN: 0167-8140; 1879-0887
• DOI: 10.1016/j.radonc.2016.02.028

Abstract Radiation-induced autophagy is believed to represent a radioprotective mechanism of cancer cells. Thus, its inhibition should support radiation treatment and increase its efficacy. On the other hand, there is evidence that radiation alone or in combination with various chemical agents can induce autophagy that results into increased cell death, especially within transformed apoptosis-resistant cells. In this paper, besides description of autophagic process and its relation to cancer and radiotherapy, we compared two contradictory radiosensitization approaches that employ inhibition and induction of autophagy. In spite of the classical concept based on cytoprotective model, there is a plethora of recently developed inducers of autophagy, which indicates the future trend in radiosensitization via modulation of autophagy. Because contemporary literature is conflicting and inconsistent in this respect, we reviewed the recent studies focused on enhancement of sensitivity of cancer cells toward radiation in regard to autophagy, revealing some striking discrepancies. The deeper the knowledge, the more complex this situation is. To interpret results of various studies correctly one has to take into account the methodology of autophagy assessment and also the fact that radiosensitization might be mediated by other than intrinsic mechanisms related to autophagy. Notwithstanding, targeting autophagy remains an attractive anti-tumor strategy.