Tumor Hypoxia and Radioresistance

Abstract

Tumor hypoxia is a prevalent feature of solid tumors, significantly contributing to increased tumor aggressiveness, metastatic potential, and resistance to conventional therapies such as radiotherapy. This review explores the complex relationship between tumor hypoxia and radioresistance, highlighting the molecular mechanisms involved and potential therapeutic strategies to enhance radiotherapy efficacy in hypoxic tumors. Key mechanisms include the role of hypoxia-inducible factors (HIFs), particularly HIF-1α, which regulates numerous genes involved in tumor survival, proliferation, and resistance under hypoxic conditions. The review also discusses the oxygen enhancement ratio (OER) and its impact on radiotherapy outcomes, emphasizing how hypoxia leads to reduced radiosensitivity by limiting the formation of radiation-induced DNA damage. Despite the development of various strategies to counteract hypoxia-induced radioresistance, such as HIF inhibitors, hypoxia-targeted gene therapy, and hypoxia-activated prodrugs (HAPs), clinical results have been mixed, necessitating further research. Additionally, advances in imaging techniques for detecting tumor hypoxia are explored, which may allow for more personalized radiotherapy approaches, such as dose painting. The future of overcoming tumor hypoxia in radiotherapy lies in the integration of innovative therapeutic strategies, personalized medicine, and improved imaging technologies, offering hope for enhanced treatment outcomes in cancer patients.