Abstract SY30-01: A wrinkle in TiME: How the aging TME drives tumor progression

Abstract

Abstract Most cancers arise after the age of 50, and the molecular mechanisms that underlie this observation are not well understood. Our overarching goal is to elucidate and target the age-related changes that drive tumor progression. We have made the seminal discovery that aged fibroblasts secrete, or stop secreting, key molecules that affect multiple aspects of tumorigenesis. Our current investigations include: the loss of molecules that maintain ECM integrity, resulting in changes in mechanotransduction and increased metastasis; the secretion of molecules that increase resistance to targeted therapy; the secretion of macromolecules such as lipids that are taken up by melanoma cells in the aged microenvironment, affecting tumor cell metabolism; changes in the aged immune tumor microenvironment; the secretion of non-canonical Wnt molecules that affect cell signaling leading to angiogenesis, metastasis, and therapy resistance. Overall, our studies indicate that the age of the mouse models we study, as well as the patients we treat must be considered in order to understand tumor progression and therapy resistance. Citation Format: Ashani T. Weeraratna. A wrinkle in TiME: How the aging TME drives tumor progression [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr SY30-01.