AUTHOR=Marwitz Sebastian , Turkowski Kati , Nitschkowski Dörte , Weigert Andreas , Brandenburg Julius , Reiling Norbert , Thomas Michael , Reck Martin , Drömann Daniel , Seeger Werner , Rabe Klaus F. , Savai Rajkumar , Goldmann Torsten TITLE=The Multi-Modal Effect of the Anti-fibrotic Drug Pirfenidone on NSCLC JOURNAL=Frontiers in Oncology VOLUME=9 YEAR=2020 URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2019.01550 DOI=10.3389/fonc.2019.01550 ISSN=2234-943X ABSTRACT=

Although immune checkpoint and targeted therapies offer remarkable benefits for lung cancer treatment, some patients do not qualify for these regimens or do not exhibit consistent benefit. Provided that lung cancer appears to be driven by transforming growth factor beta signaling, we investigated the single drug potency of Pirfenidone, an approved drug for the treatment of lung fibrosis. Five human lung cancer cell lines and one murine line were investigated for transforming growth factor beta inhibition via Pirfenidone by using flow cytometry, In-Cell western analysis, proliferation assays as well as comprehensive analyses of the transcriptome with subsequent bioinformatics analysis. Overall, Pirfenidone induced cell cycle arrest, down-regulated SMAD expression and reduced proliferation in lung cancer. Furthermore, cell stress pathways and pro-apoptotic signaling may be mediated by reduced expression of Survivin. A murine subcutaneous model was used to assess the in vivo drug efficacy of Pirfenidone and showed reduced tumor growth and increased infiltration of T cells and NK cells. This data warrant further clinical evaluation of Pirfenidone with advanced non-small cell lung cancer. The observed in vitro and in vivo effects point to a substantial benefit for using Pirfenidone to reactivate the local immune response and possible application in conjunction with current immunotherapies.