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

Grant Number: 3R00CA218686-04
PI Name: Da Silva Gomes
Project Title: Vitamin B12 supplementation as novel therapeutic strategy to improve cancer-associated outcomes

Abstract: 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. PUBLIC HEALTH RELEVANCE: Despite aging being the main risk factor for cancer with the average age of diagnosis at 66, the framework of cancer research that factors in the aging process is very slim. Vitamin deficiencies, including vitamin B12 deficiency, are known to occur with aging and have metabolic consequences to the hosts and therefore can affect the tumorigenic process. Here, we aim to understand how vitamin B12 supplementation influence the tumorigenic process. Results will reveal if vitamin B12 supplementation is a good and safe therapeutic intervention to ameliorate cancer prognosis, particularly in the most susceptible and vulnerable population, the elderly.

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