Autophagy and ionizing radiation in tumors: The “survive or not survive” dilemma

Abstract

Autophagy is a so-called "self-eating" system responsible for degrading long-lived proteins and cytoplasmic organelles, whose products are recycled to maintain cellular homeostasis. This ability makes autophagy a good candidate for a survival mechanism in response to several stresses, including the tumor cell transformation. In particular, recent studies suggested that autophagy functions as a pro-death mechanism within different tumor contexts. It is, however, widely reported that autophagy represents both a survival mechanism or contributes directly to cell death fate. This interplay of the autophagy functions has been observed in many types of cancers and, in some cases, autophagy has been demonstrated to both promote and inhibit antitumor drug resistance. From a therapeutical point of view, the effects of the modulation of the tumor cell autophagic status, in response to ionizing radiations, are presently of particular relevance in oncology. Accordingly, this review also provides a perspective view on future works for exploring the modulation of autophagic indices in tumor cells as a novel molecular-based adjuvant strategy, in order to improve radiotherapy and chemotherapy effects in cancer patients.

microRNA-17 regulates the expression of ATG7 and modulates the autophagy process, improving the sensitivity to temozolomide and low-dose ionizing radiation treatments in human glioblastoma cells

“…1 Several researches are now directed toward the dissection of the autophagic pathway in order to identify novel potential targets, effective in the regulation of the autophagy process, and to enhance the ratio of cell death induction, combining gene therapy to traditional protocols. [7][8][9] In particular, microRNAs (miRNAs) are small non coding RNAs that have been estimated to regulate more than 60% of all mammal protein-coding genes. 10 They are mainly known as cytoplasmic post-transcriptional regulators of gene expression, inhibiting protein synthesis by base-pairing to target mRNA in their 3'-UTR and leading to mRNA decay or destabilization.…”

NVP-BEZ-235 enhances radiosensitization via blockade of the PI3K/mTOR pathway in cisplatin-resistant non-small cell lung carcinoma.

“…Autophagy, the phenomenon of cellular self-digestion, has the potential to promote either cell death or cell survival in the context of different cancers [12-14] and post-irradiation [13, 15]. At baseline, it contributes to the health of the cell by recycling non-useful compounds, including damaged organelles and cytotoxic aggregates, and can be upregulated in response to cellular stress to combat infection or increase survival in suboptimal growth conditions [12-14].…”

Réirradiation de métastases ganglionnaires d’un adénocarcinome œsogastrique par une technique de tomothérapie associée à de l’évérolimus

“…La protéine mTor, lorsqu'elle est activée, inhibe l'autophagie alors que son inactivation la favorise [14]. Par ailleurs, l'autophagie étant une voie de mort cellulaire radioinduite, les inhibiteurs de mTor sont susceptibles de sensibiliser les cellules tumorales à la radiothérapie [15]. La rapamycine induit ainsi une radiosensibilisation dans des modèles de gliome [8].…”