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

项目总结 虽然癌症是一种老年人的疾病，但伴随着衰老过程的深刻变化 在肿瘤形成过程的研究或治疗方法的开发中很少考虑 治疗癌症的策略。因此，全面了解生物体是如何 需要随着年龄的增长而重新编程，以刺激更有效的发展 可改善癌症患者生活质量和预后的治疗策略和干预措施 平均年龄的患者。我们之前已经确认循环甲基丙二酸是一种 随着年龄的增长而积累的共生代谢产物，至少在一定程度上调节了 老年人的肿瘤进展速度加快。通过资助的研究 父母奖，我们发现甲基丙二酸发挥其促进攻击性的作用 通过直接对癌细胞重新编程以及间接通过抑制T细胞和 从而促进免疫逃避。甲基丙二酸在健康人群中的蓄积 个人主要归因于维生素B12缺乏，这在老年人中很常见 人民。在这一补充中，我们假设纠正旧宿主中的维生素B12将恢复 甲基丙二酸增加到生理水平，从而影响肿瘤的形成过程。 因此，在这项应用中，我们将在老年宿主中补充维生素B12，并评估1)维生素 在老年宿主中补充B12可以抑制癌症进展；2)如果维生素B12 补充剂可改善T细胞的渗透和功能。

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.