Lung cancer is the leading cause of cancer death in the United States. Due to limited efficacy of current conventional chemotherapy, the majority of patients face poor prognosis and eventually succumb the disease. Therefore, the study of combination therapy using traditional anticancer drugs with novel therapeutic approaches is needed. Pirfenidone is a small molecule that is being used in Phase II and III clinical trials for idiopathic pulmonary fibrosis (IPF). Although it has already been approved for IPF in Europe, there is no known mechanism of action known for the drug. Recently we discovered that Pirfenidone has a detrimental effect on cancer associated fibroblasts (CAFs) as well as in non-small cell lung cancer (NSCLC) cells. Our hypothesis is that Pirfenidone, in combination with standard chemotherapy, will act synergistically and proffer a more potent therapeutic strategy for NSCLC. Our studies show that in a co-culture model there is a decrease in viability on CAFs and NSCLC cells when the combination of Pirfenidone and Cisplatin is used. Furthermore, Pirfenidone and Cisplatin were able to have an anti-tumor effect in a xenograft model of NSCLC and CAFs. In addition, insights in the mechanism by which Pirfenidone and Cisplatin induce synergy in NSCLC cells are being elucidated. Our studies show that the combination of drugs leads to an increase in phosphorylated ERK as well as a decrease in phosphorylated Akt. Thus, involving the PI3K and MAPK/ERK pathways in Pirfenidone/Cisplatin induced cell death. Our lab is the first to recognize the therapeutic potential of combining Pirfenidone and Cisplatin, as well as elucidating the mechanism of action for both drugs in NSCLC.

Citation Format: Melanie Mediavilla-Varela, David Noyes, Kingsley Boateng, Scott Antonia. Combination of Pirfenidone and Cisplatin as a potential therapeutic strategy in NSCLC. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1704. doi:10.1158/1538-7445.AM2014-1704