Medicine and Health Sciences Commons^™

Pparα And Pparγ Activation Is Associated With Pleural Mesothelioma Invasion But Therapeutic Inhibition Is Ineffective, M. Lizeth Orozco Morales, Catherine A. Rinaldi, Emma De Jong, Sally M. Lansley, Joel P. A. Gummer, Bence Olasz, Shabarinath Nambiar, Danika E. Hope, Thomas H. Casey, Y. C. Gary Lee, Connull Leslie, Gareth Nealon, David M. Shackleford, Andrew K. Powell, Marina Grimaldi, Patrick Balaguer, Rachael M. Zemek, Anthony Bosco, Matthew J. Piggott, Alice Vrielink, Richard A. Lake, W. Joost Lesterhuis

Research outputs 2022 to 2026

Mesothelioma is a cancer that typically originates in the pleura of the lungs. It rapidly invades the surrounding tissues, causing pain and shortness of breath. We compared cell lines injected either subcutaneously or intrapleurally and found that only the latter resulted in invasive and rapid growth. Pleural tumors displayed a transcriptional signature consistent with increased activity of nuclear receptors PPARα and PPARγ and with an increased abundance of endogenous PPAR-activating ligands. We found that chemical probe GW6471 is a potent, dual PPARα/γ antagonist with anti-invasive and anti-proliferative activity in vitro. However, administration of GW6471 at doses that provided sustained plasma …