Radiation-activated prosurvival signaling pathways in cancer cells

Radiation therapy is a standard treatment for local disease control of solid tumors. Although radiation therapy has significantly improved the overall survival and quality of life of cancer patients, its efficacy has been limited by the development of radiation resistance and the presence of residual disease after therapy, leading to cancer recurrence. Radiation induces cytotoxicity in cancer cells, mainly by causing DNA damage. However, concurrently radiation can also activate multiple protective signaling pathways, such as ataxia telangiectasia mutated/ataxia telangiectasia mutated and Rad3-related protein, phosphoinositide-3-kinase/protein kinase B, extracellular signal-regulated kinase, and nuclear factor-κB, which promote cell cycle checkpoint activation, leading to cell cycle arrest/DNA repair and inhibition of apoptosis. Conjointly, these signaling pathways protect cancer cells by reducing the magnitude of radiation-induced cytotoxicity and promoting radioresistance of cancer cells. Thus, targeting these prosurvival pathways could have great potential for sensitizing cancer cells to radiation therapy. In the present review, we summarize the current literature on the radiation-activated prosurvival signaling pathways that promote radioresistance.