{Reference Type}: Journal Article
{Title}: Rosiglitazone and trametinib exhibit potent anti-tumor activity in a mouse model of muscle invasive bladder cancer.
{Author}: Plumber SA;Tate T;Al-Ahmadie H;Chen X;Choi W;Basar M;Lu C;Viny A;Batourina E;Li J;Gretarsson K;Alija B;Molotkov A;Wiessner G;Lee BHL;McKiernan J;McConkey DJ;Dinney C;Czerniak B;Mendelsohn CL;
{Journal}: Nat Commun
{Volume}: 15
{Issue}: 1
{Year}: 2024 Aug 2
{Factor}: 17.694
{DOI}: 10.1038/s41467-024-50678-2
{Abstract}: 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.