In our laboratory, we utilize in vitro and in vivo models incorporated with quantitative approaches to identify novel mechanisms involved in the acquired tumor resistance to multikinase inhibitors, and delineate the mechanistic basis for rational design of combined therapies with two or more targeted therapeutic agents to enhance the anti-cancer efficacy and reduce the dose-limited toxicity. The PI has been actively engaged in experimental cancer therapy research for the past 15 years. The PI’s direct involvements in this area include: 1) Mechanistic study of acquired tumor resistance to multikinase inhibitors in KRAS-mutant non-small cell lung carcinoma (NSCLC), 2) Rational design of targeted combination therapies, and 3) Preclinical PKPD evaluation of anticancer therapeutic agents.

Acquired Resistance to Multi-Kinase Inhibitors in Lung Cancer
(Funded by TCOP Internal Seed Grant)

This project was concerned with exploring mechanisms involved in the acquired multikinase inhibitor (MKI) resistance using an in vivo drug resistance tumor model. The proposed approach was demonstrated for sorafenib in a human NSCLC xenograft model in athymic nude mice. The findings of this study provided a mechanistic basis for the rational design of combination therapy that would overcome MKI resistance and achieve durable antitumor effects.