Novel Approach to Targeted Therapy in NSCLC
Posted: Friday, January 19, 2018
The use of patient-derived fibroblast (PDF) cell lines may be employed to identify mechanisms that contribute to resistance in non–small cell lung cancer (NSCLC), according to Haichuan Hu, MD, of the Massachusetts General Hospital Cancer Center and Harvard Medical School, and colleagues. The study, presented by Dr. Hu at the recent American Association for Cancer Research–International Association for the Study of Lung Cancer (AACR-IASLC) International Joint Conference: Lung Cancer Translational Science from the Bench to the Clinic (Abstract PR04), utilized PDF models to successfully identify nonautonomous resistance mechanisms in the tumor microenvironment.
In this study, the investigators established cancer-associated fibroblast cell lines from individual EGFR-mutant NSCLC biopsies. They screened these cell lines for nonautonomous resistance by co-culturing patient-derived cancer models and PDF models in vitro. To further identify mechanisms of this type of resistance, they tested the samples using a drug screen to determine the pathway for the cancer cells’ survival and an analysis to identify which cytokine(s) are responsible.
Using these methods, the team of investigators identified both the canonical hepatocyte growth factor (HGF)-dependent and HGF-independent mechanisms that contribute to EGFR tyrosine kinase inhibitor resistance, which can both be explained by the variable cytokine expression in each cell line.
This novel approach provides a new way to guide pharmacotherapy, and using PDFs in the future "will be valuable to optimize targeted therapy and to inform the design of personalized pharmaceutical interventions," concluded Dr. Hu and colleagues.
