Drug Sensitivity Signatures

Identifying Molecular Predictive Biomarkers for Available Chemotherapy and Targeted Therapy for Lung Cancer

We have assembled the world’s largest dataset of drug response phenotypes for ~100 NSCLC cell lines to drugs already used for lung cancer treatment. We have identified important subsets (10-20 percent) of lung cancers that are very sensitive to these therapies compared to others that are 1000-fold more resistant.

We are integrating this with our genome-wide information in mRNA expression, copy number variation, DNA methylation, proteomics, and whole exome mutation analyses to identify molecular biomarkers predictive of response to these clinically available drugs. This provides a preclinical platform for developing and testing new lung cancer therapies and also a method for developing molecular “enrollment biomarkers” that can be used in clinical trials.

In collaboration with Dr. Ignacio Wistuba in MD Anderson Cancer Center, we profiled 275 lung cancer specimens with drug response information to test the clinical relevance of the tumor cell line signatures.

Additionally, we are working with UT Southwestern scientists and clinicians Pier Paolo Scaglioni, M.D., Joan Schiller, M.D., and David Gerber, M.D. to develop rationale targeted therapy for KRAS mutant lung cancer. We are working to develop all of the preclinical information and CLIA-certified tests to bring this new personalized medicine approach to the clinic.