Vitamin B12 supplementation as novel therapeutic strategy to improve cancer-associated outcomes

点击翻译按钮获取中文摘要

PROJECT SUMMARY While cancer is a disease of the old, the profound alterations that accompany the aging process are rarely considered in the study of the tumorigenic process or in the development of therapeutic strategies to treat cancer. Thus, a comprehensive understanding of how the organismal reprogramming that occur with age is needed to spur the development of more effective therapeutic strategies and interventions that can ameliorate quality of life and outcome of cancer patients of average age. We have previously identified circulatory methylmalonic acid as an oncometabolite whose accumulation occurs with age and mediates, at least in part, the accelerated pace of tumor progression that occurs in old people. Through the research funded by the parent award, we have discovered that methylmalonic acid exerts its pro-aggressive effects by directly reprogramming cancer cells as well as indirectly by suppressing T cells and consequently promoting immune evasion. Methylmalonic acid accumulation in otherwise healthy individuals has been mostly attributed to vitamin B12 deficiency, a common occurrence in older people. In this supplement, we hypothesize that correcting vitamin B12 in old hosts will restore methylmalonic acid to physiological levels and consequently affect the tumorigenic process. Therefore, in this application we will supplement vitamin B12 in old hosts and evaluate if 1) vitamin B12 supplementation in old hosts suppresses cancer progression; and 2) if vitamin B12 supplementation improves T cell infiltration and function.