2017 Lung Cancer Research Foundation Annual Grant Program
Triparna Sen, PhD
The University of Texas MD Anderson Cancer Center
Research Project:
Investigating the role of DNA damage repair inhibition in enhancing anti-tumor immunity in small cell lung cancer
Summary:
Small cell lung cancer (SCLC) is an aggressive form of lung cancer that accounts for 14% of lung cancer cases. Despite decades of active research, treatment options for SCLC are limited. Recent efforts to expand the therapeutic arsenal toward SCLC have focused in part on immunotherapy, particularly immune checkpoints inhibitors, which are drugs that unleashes an immune system attack on cancer cells. However, overall response rates to immune checkpoint blockade remain poor. DNA damage repair (DDR) proteins helps a cell identify and correct damage to the DNA molecule. Drugs that target these DDR proteins like PARP and CHK1 have provided exciting new therapeutic options for the treatment of SCLC. Recent clinical data illustrating that defective DDR, predicts improved response to immune checkpoint blockade (anti-PD-1) supports the hypothesis that the addition of a DDR inhibitor to an immune checkpoint inhibitor may significantly enhance response rates and outcomes. This proposal seeks to study the key interactions between DDR targeting and anti-tumor immune response in SCLC. Dr. Sen will leverage a large, integrated set of laboratory and patient samples that will significantly accelerate and magnify the potential impact of the work. At completion, this study will- (1) Improve mechanistic understanding of how targeting DDR enhances anti-tumor immune response; (2) Identify of novel immunotherapy combinations; and (3) Detect biomarkers to identify SCLC patients who will most likely respond to DDR+ immunotherapy combinations. The goal is to translate this approach for improved treatment options of SCLC patients.