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

维生素 B12 补充剂作为改善癌症相关结果的新型治疗策略

基本信息

批准号：
10509128
负责人：
Ana da silva Gomes
金额：
$ 16.85万
依托单位：
H. LEE MOFFITT CANCER CTR & RES INST
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-09-10 至 2023-08-31
项目状态：
已结题

项目摘要

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.

项目摘要尽管癌症是旧的疾病，但伴随衰老过程的深刻改变在肿瘤过程或治疗性的发展中很少考虑治疗癌症的策略。因此，对生物如何的全面理解需要随年龄进行重新编程以刺激更有效的发展可以改善癌症生活质量和结果的治疗策略和干预措施平均年龄的患者。我们先前已经确定循环甲基丙二酸 oncometabolite的积累是随着年龄的增长而发生的，至少在某种程度上是老年人发生的肿瘤进展的加速速度。通过由父母奖，我们发现甲基丙二酸会发挥其促进作用通过抑制T细胞和因此促进免疫逃避。甲基丙二酸在其他健康中的积累个体主要归因于维生素B12缺乏症，这是老年人的常见发生人们。在这种补充中，我们假设在旧宿主中纠正维生素B12将恢复甲基丙二酸达到生理水平，因此会影响致癌过程。因此，在此应用中，我们将在旧宿主中补充维生素B12，并评估1）维生素旧宿主中补充的B12抑制癌症的进展； 2）如果维生素B12 补充可改善T细胞浸润和功能。