Abstract IA018: Breaking the obesity-endometrial cancer link: Lessons from preclinical studies

Abstract

Abstract The prevalence of obesity, an established risk factor for endometrial cancer, has increased dramatically over the past 50 years in the US and many other countries. Relative to normoweight cancer patients, obese cancer patients also often have poorer prognoses, resistance to chemotherapies, and are more likely to develop distant metastases. Recent progress on elucidating the mechanisms underlying the obesity-cancer connection suggests that obesity exerts pleomorphic effects on pathways related to tumor development and progression, and thus there are multiple opportunities for primary to tertiary prevention of obesity-related endometrial cancers. We now know that obesity can impact each of the well-established hallmarks of cancer, but obesity-associated perturbations in systemic metabolism and inflammation, and the interactions of these perturbations with cancer cell energetics and immune response, are emerging as the primary drivers of obesity-associated endometrial cancer development and progression. While additional work is needed on the mechanisms underlying the obesity-endometrial cancer link, research is also urgently needed on how to best mitigate the procancer effects of obesity on the endometrium, as well as ways to prevent obesity-associated metastatic progression and therapeutic resistance. We will thus discuss relevant dietary and lifestyle interventions that are being implemented in preclinical and clinical trials, with the ultimate goal of reducing incidence and progression of obesity-associated endometrial cancer. Citation Format: Stephen D. Hursting. Breaking the obesity-endometrial cancer link: Lessons from preclinical studies [abstract]. In: Proceedings of the AACR Virtual Special Conference: Endometrial Cancer: New Biology Driving Research and Treatment; 2020 Nov 9-10. Philadelphia (PA): AACR; Clin Cancer Res 2021;27(3_Suppl):Abstract nr IA018.