Abstract 4948: Pirfenidone as a potential therapeutic treatment for CAFs and cancer cells in NSCLC.

Abstract

Abstract 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. Until recently, the main focus in cancer research has been targeting the neoplastic cell. However, the importance of the tumor microenvironment, including cancer associated fibroblasts (CAFs), in cancer progression is now clear and targeting both, the neoplastic cell as well as the CAF, is being recognized as an important therapeutic approach. We have recently discovered that pirfenidone might be the drug to target these cells. Pirfenidone is a small molecule that has been shown to decrease fibrosis in a variety of fibrotic diseases. The exact mechanism responsible for its anti-fibrotic effects remains to be elucidated. Our hypothesis is that pirfenidone (by targeting the CAFs) in combination with standard chemotherapy (by targeting the cancer cells) will act synergistically and proffer a more potent therapeutic strategy for non-small cell lung cancer (NSCLC). Our studies show that in the presence of pirfenidone NSCLC associated CAF viability decreases in vitro. Furthermore, pirfenidone was able to induce apoptotic cell death as well as cell cycle arrest in NSCLC associated CAFs. In addition, we were able to observe that CAFs treated with pirfenidone decreased active TGFβ when compared to the control. Moreover, in a spheroid model, pirfenidone was able to affect the crosstalk between the cancer cells and CAFs leading to increased apoptosis and decreased viability. Currently, pirfenidone is being used in Phase II and III clinical trials for idiopathic pulmonary fibrosis. Our lab is the first one to recognize the potential of pirfenidone as a potential treatment of NSCLC. Citation Format: Melanie Mediavilla-Varela, Kimberly Luddy, David Noyes, Kingsley Boateng, Scott Antonia. Pirfenidone as a potential therapeutic treatment for CAFs and cancer cells in NSCLC. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4948. doi:10.1158/1538-7445.AM2013-4948