%0 Journal Article
%T Rosiglitazone and trametinib exhibit potent anti-tumor activity in a mouse model of muscle invasive bladder cancer.
%A Plumber SA
%A Tate T
%A Al-Ahmadie H
%A Chen X
%A Choi W
%A Basar M
%A Lu C
%A Viny A
%A Batourina E
%A Li J
%A Gretarsson K
%A Alija B
%A Molotkov A
%A Wiessner G
%A Lee BHL
%A McKiernan J
%A McConkey DJ
%A Dinney C
%A Czerniak B
%A Mendelsohn CL
%J Nat Commun
%V 15
%N 1
%D 2024 Aug 2
%M 39095358
%F 17.694
%R 10.1038/s41467-024-50678-2
%X Muscle invasive bladder cancers (BCs) can be divided into 2 major subgroups-basal/squamous (BASQ) tumors and luminal tumors. Since Pparg has low or undetectable expression in BASQ tumors, we tested the effects of rosiglitazone, Pparg agonist, in a mouse model of BASQ BC. We find that rosiglitazone reduces proliferation while treatment with rosiglitazone plus trametinib, a MEK inhibitor, induces apoptosis and reduces tumor volume by 91% after 1 month. Rosiglitazone and trametinib also induce 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.