Radiotherapy (RT) is a cancer treatment that uses high doses of radiation to kill cancer cells and shrink tumors. Although great success has been achieved on radiotherapy, there is still an intractable challenge to enhance radiation damage to tumor tissue and reduce side effects to healthy tissue. Radiosensitizers are chemicals or pharmaceutical agents that can enhance the killing effect on tumor cells by accelerating DNA damage and producing free radicals indirectly. In most cases, radiosensitizers have less effect on normal tissues. In recent years, several strategies have been exploited to develop radiosensitizers that are highly effective and have low toxicity. In this review, we first summarized the applications of radiosensitizers including small molecules, macromolecules, and nanomaterials, especially those that have been used in clinical trials. Second, the development states of radiosensitizers and the possible mechanisms to improve radiosensitizers sensibility are reviewed. Third, the challenges and prospects for clinical translation of radiosensitizers in oncotherapy are presented.

change) > = 1. VIP values were extracted from OPLS-DA result, which also contains score plots and permutation plots, generated using R package MetaboAnalystR. The data was log transform (log2) and mean centering before OPLS-DA. To avoid overfitting, a permutation test (200 permutations) was performed.Statistical Analyses: One-way and two-way analyses of variance (ANOVA) and t-tests were used to determine statistical significance (*p < 0.05, **p < 0.01, ***p < 0.001); p-value less than 0.05 was considered statistically significant.

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