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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.

项目摘要虽然癌症是老年人的疾病，但伴随着衰老过程的深刻变化在肿瘤发生过程的研究或治疗药物的开发中很少考虑治疗癌症的策略。因此，全面了解生物体如何随着年龄的增长，需要重新编程，以刺激更有效的可以改善生活质量和癌症结局的治疗策略和干预措施平均年龄的患者。我们以前已经确定循环甲基丙二酸是一种癌代谢物，其积累随着年龄的增长而发生，并至少部分介导老年人肿瘤进展的加速。通过研究资助由在父母奖上，我们发现甲基丙二酸发挥了它的促攻击作用，通过直接重编程癌细胞以及间接抑制T细胞，从而促进免疫逃避。甲基丙二酸在其他健康人群中蓄积维生素B12缺乏症是老年人中常见的一种疾病。人在这个补充，我们假设，纠正维生素B12在旧主机将恢复甲基丙二酸达到生理水平，从而影响肿瘤发生过程。因此，在本申请中，我们将在老年宿主中补充维生素B12，并评估1）维生素B12是否在老年宿主中补充B12可抑制癌症进展; 2）如果维生素B12 补充改善T细胞浸润和功能。