2015 Lung Cancer Research Foundation Annual Grant Program
Benjamin Izar, MD, PhD
Dana-Farber Cancer Institute
Research Project:
Understanding treatment resistance in lung cancer using a novel gene testing approach
Summary:
Lung tumors are complex tissues that contain heterogeneous malignant cell populations and various non-malignant cells that form the tumor ecosystem. Current profiling methods are performed on RNA or DNA isolated from whole pieces of tissue. These represent mixtures of RNA/DNA that are not able to recapitulate the inherent heterogeneity that exist in a tumor. Increasingly effects of various cell populations and the tumor microenvironment are recognized as important drivers of resistance to targeted cancer therapies, for example EGFR-inhibitors in EGFR-mutated non-small cell lung cancer. To overcome some of these barriers, Dr. Izar will apply single-cell RNA-sequencing to malignant and non-malignant cells isolated from freshly procured EGFR-inhibitor resistant patient samples. Using this approach, Dr. Izar and his team can directly measure intra- and inter-tumor heterogeneity, profile the tumor ecosystem, and potential interaction among various cell components at an unprecedented cell-to-cell resolution. In doing so, they hope to gain insights into transcriptional programs and interactions that contribute to resistance mechanisms to EGFR-inhibitors, and open new avenues for therapeutic development.