Despite the increasing clinical application of radiotherapy, the resistance of tumor cells to IR remains a significant obstacle, potentially leading to relapse, a poor treatment response or poor prognosis.

Currently, approximately 60% of patients being treated for cancer in the United States have received radiotherapy. It can be used to eradicate certain cancers or reduce their likelihood of recurrence, and as a palliative treatment.

Radiotherapy is defined as the clinical use of ionizing radiation (IR), including α or γ rays, to induce DNA damage in all exposed cells to ultimately kill cancer cells or prevent cancer growth. Numerous treatments are available for non-melanoma skin cancer patients, with radiotherapy being an efficacious and tissue-preserving non-surgical option. In 2018, 18.1 million new cancer cases, and 9.6 million deaths from cancer, were reported worldwide. In 2017, the global death population caused by cancer reached 9 million, which was nearly twice the number in 1990. A better understanding of the relationships among vitamin D, the gut microbiota, and radiotherapy outcomes will shed more light on radiation resistance, and also promote the development of new strategies for overcoming it, thus addressing an important challenge associated with the currently available radiotherapy modalities for cancer patients.

Our understanding of the contribution of vitamin D and the gut microbiota to radiotherapy outcomes has been increasing gradually. Alteration of vitamin D level influences the patient response to radiotherapy, where the underlying mechanisms may be associated with the intestinal microenvironment, immune molecules in the intestines, gut microbiome metabolites, and signaling pathways associated with vitamin D receptors. Radiotherapy changes the composition of the gut microbiota, which in turn influence the serum level of vitamin D, and its distribution and metabolism in the body. A hypothesis is developed to describe the relationships among vitamin D, the gut microbiota, and radiotherapy outcomes. Against this background, this paper reviewed research regarding the associations among vitamin D, microbiota dysbiosis, and radiation resistance. Vitamin D is an important supplement for cancer patients treated with radiotherapy. Increasing evidence indicates that the human gut microbiome plays a role in the development of radiation resistance. Radiation resistance is a serious issue in radiotherapy.

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