Radiosensitization of tumor cells

Radiosensitization of tumor cells refers to the use of agents or approaches that increase the susceptibility of cancer cells to ionizing radiation. Radiosensitizers act through several core mechanisms: enhancing DNA damage or blocking its repair, perturbing cell-cycle checkpoints to trap cells in radiosensitive phases, and overcoming tumor hypoxia to amplify radiation-induced free radical formation. Clinically used or studied radiosensitizing strategies include conventional chemotherapies (fluoropyrimidines, gemcitabine, platinums), targeted inhibitors of growth factor signaling (e.g., EGFR/RTK pathway, Raf–MEK–ERK, PI3K–AKT–mTOR), DNA repair inhibitors (e.g., PARP inhibitors), and hypoxia-directed agents (nitroimidazoles, tirapazamine). Predictors of response include features of the DNA damage response (ATM/ATR/CHK, DNA-PKcs), p53 pathway status, and tumor hypoxia. While many agents radiosensitize tumors in preclinical models and some are used clinically with radiotherapy, toxicity and limited clinical evidence constrain broader application for certain experimental classes.

Other names

radiosensitizerradiation sensitizerradio-enhancertumor radiosensitization

Inhibit DNA repair (e.g., crosslinking by platinums; PARP inhibition), increasing radiation-induced DNA damage; Force inappropriate S-phase progression/dysregulate S-phase checkpoints (fluoropyrimidines, gemcitabine), leading to misrepair of radiation damage; Arrest cells in radiosensitive phases (e.g., G2/M via taxanes); Modify hypoxia to enhance oxygen-dependent free radical formation (oxygen mimetics like nitroimidazoles; oxygen delivery approaches); Inhibit growth factor receptor signaling and downstream pathways that promote radioresistance (EGFR/RTKs, Raf–MEK–ERK, PI3K–AKT–mTOR)