Abstract A027: The role of nuclear receptors as promoters of luminal tumors and suppressors of basal/squamous tumors

Abstract

Abstract Bladder cancers (BCs) can be divided into 2 major subgroups, basal/squamous (BASQ) tumors that are muscle invasive and luminal tumors which are relatively benign. Pparg, has been suggested to act as a tumor suppressor in BASQ tumors, where its expression is low or undetectable. Here we tested the effects of rosiglitazone, Pparg agonist in a mouse model of BASQ BC. We find that rosiglitazone alone, reduced proliferation but did not decrease tumor volume, while treatment with rosiglitazone plus trametinib, a MEK inhibitor induced apoptosis and reduced tumor volume by 91% after 1 month. Rosiglitazone and trametinib also induced a shift from BASQ to luminal differentiation in tumors, which our analysis suggests is mediated by retinoid signaling, a pathway known to drive the luminal differentiation program. Our data suggest that rosiglitazone, trametinib, and retinoids, which are all FDA approved, may be clinically active in BASQ tumors in patients. Citation Format: Cathy L. Mendelsohn, Sakina A. Plumber, Tiffany Tate. The role of nuclear receptors as promoters of luminal tumors and suppressors of basal/squamous tumors [abstract]. In: Proceedings of the AACR Special Conference on Bladder Cancer: Transforming the Field; 2024 May 17-20; Charlotte, NC. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(10_Suppl):Abstract nr A027.