Radiation therapy (RT) is often given concurrently with systemic chemotherapy in order to sensitize the cancer cells to radiation and increase local and regional disease control. However, chemotherapy is often associated with significant toxicity and many patients cannot tolerate it. As such, exploring alternative approaches to radiosensitization that may be more tolerable for patients is important. One innovative strategy that has potential to enhance both the safety and efficacy of SBRT is a methionine-restricted diet (MRD) as an adjunct to radiation therapy. While normal cells can tolerate some degree of methionine deficiency, the vast majority of cancer cells are methionine auxotrophs that require dietary intake of methionine. In the absence of methionine, cancer cells undergo cell cycle arrest and cell death. Preclinical data suggests that consuming a reduced quantity of methionine sensitizes cancer cells to radiation therapy and reduces metastasis formation and disease progression in mice; Phase 1 clinical trials have also demonstrated the safety of the diet with and without concurrent chemotherapy; however, dietary restriction of methionine has not been tested in combination with radiation therapy in humans. This protocol will test our hypothesis that a MRD will be a safe addition to radiation therapy for a variety of human malignancies.
A diet consisting of a reduced quantity of the essential amino acid methionine sensitizes cancer cells to radiation therapy and reduces metastasis formation and disease progression in mice. However, to date, dietary restriction of methionine has not been tested in combination with radiation therapy in humans as a strategy to improve patient outcomes.