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Rosiglitazone and trametinib exhibit potent anti-tumor activity in a mouse model of muscle invasive bladder cancer

Author

Listed:
  • Sakina A. Plumber

    (Columbia University Irving Medical Center)

  • Tiffany Tate

    (Columbia University Irving Medical Center
    Generation Bio)

  • Hikmat Al-Ahmadie

    (Memorial Sloan Kettering Cancer Center)

  • Xiao Chen

    (Columbia University Irving Medical Center
    Shandong University)

  • Woonyoung Choi

    (Johns Hopkins Greenberg Bladder Cancer Institute)

  • Merve Basar

    (Columbia University Irving Medical Center
    Harvard Medical School)

  • Chao Lu

    (Columbia University Irving Medical Center)

  • Aaron Viny

    (Columbia University Irving Medical Center)

  • Ekatherina Batourina

    (Columbia University Irving Medical Center)

  • Jiaqi Li

    (Columbia University Irving Medical Center)

  • Kristjan Gretarsson

    (Columbia University Irving Medical Center)

  • Besmira Alija

    (Columbia University Irving Medical Center)

  • Andrei Molotkov

    (Columbia University Irving Medical Center)

  • Gregory Wiessner

    (Columbia University Irving Medical Center)

  • Byron Hing Lung Lee

    (The University of Texas MD Anderson Cancer Center)

  • James McKiernan

    (Columbia University Irving Medical Center)

  • David J. McConkey

    (Johns Hopkins Greenberg Bladder Cancer Institute)

  • Colin Dinney

    (The University of Texas MD Anderson Cancer Center)

  • Bogdan Czerniak

    (The University of Texas MD Anderson Cancer Center)

  • Cathy Lee Mendelsohn

    (Columbia University Irving Medical Center)

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.

Suggested Citation

  • Sakina A. Plumber & Tiffany Tate & Hikmat Al-Ahmadie & Xiao Chen & Woonyoung Choi & Merve Basar & Chao Lu & Aaron Viny & Ekatherina Batourina & Jiaqi Li & Kristjan Gretarsson & Besmira Alija & Andrei , 2024. "Rosiglitazone and trametinib exhibit potent anti-tumor activity in a mouse model of muscle invasive bladder cancer," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
  • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-50678-2
    DOI: 10.1038/s41467-024-50678-2
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    References listed on IDEAS

    as
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