Abstract IA022: Age-induced metabolic reprogramming: A bridge between the aging process and tumorigenesis

Abstract

Abstract Lung cancer accounts for the largest number of cancer-associated deaths in the United States. While great strides have been made due to the introduction of immunotherapies and targeted therapies against oncogenic drivers, chemotherapies remain the standard of care for the majority of lung cancer patients. However, many patients do not respond to these treatments or relapse following an initial response. We postulate that part of the problem is the lack of consideration in preclinical research and clinical trials of the main driver of lung tumorigenesis, the aging process. Here, we show that the organismal metabolic reprogramming that occurs with aging endows cancer cells with pro-aggressive properties favoring progression into metastatic disease through, at least in part, the accumulation in the circulation of methylmalonic acid, a by-product of vitamin B12 deficiency. On the other hand, we also show that this age-induced organismal metabolic reprogramming makes lung tumors intrinsically more resistant to chemotherapies through the chronic upregulation of glucocorticoid hormones. Together, our work demonstrates a role for age-induced systemic metabolic reprogramming in shaping the tumorigenic process toward more aggressive, treatment-resistant disease and offers a rationale for using interventions that ameliorate the metabolic deregulation that occurs with age in the treatment of age-related cancers. Citation Format: Ana P. Gomes. Age-induced metabolic reprogramming: A bridge between the aging process and tumorigenesis [abstract]. In: Proceedings of the AACR Special Conference: Aging and Cancer; 2022 Nov 17-20; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2022;83(2 Suppl_1):Abstract nr IA022.