Unraveling Mitochondrial Determinants of Tumor Response to Radiation Therapy

Radiotherapy represents a highly targeted and efficient treatment choice in many cancer types, both with curative and palliative intents. Nevertheless, radioresistance, consisting in the adaptive response of the tumor to radiation-induced damage, represents a major clinical problem. A growing body of the literature suggests that mechanisms related to mitochondrial changes and metabolic remodeling might play a major role in radioresistance development. In this work, the main contributors to the acquired cellular radioresistance and their relation with mitochondrial changes in terms of reactive oxygen species, hypoxia, and epigenetic alterations have been discussed. We focused on recent findings pointing to a major role of mitochondria in response to radiotherapy, along with their implication in the mechanisms underlying radioresistance and radiosensitivity, and briefly summarized some of the recently proposed mitochondria-targeting strategies to overcome the radioresistant phenotype in cancer.

Automated summary

Radiotherapy is an effective and targeted treatment option for many cancer types, but radioresistance remains a clinical challenge. Recent studies suggest that mechanisms related to mitochondrial changes and metabolic remodeling play an important role in the development of radioresistance. This article discusses the main contributors to acquired cellular radioresistance and their relation to mitochondrial changes, and summarizes some recently proposed mitochondria-targeting strategies to overcome radioresistant phenotypes in cancer.