Research Summary: PARP1 as a novel therapeutic target in small cell lung cancer

Grant Recipient: Dr. Lauren A. Byers
Title of Project: PARP1 as a novel therapeutic target in small cell lung cancer
Sponsoring Institution: University of Texas M.D. Anderson Cancer Center

There is an urgent, unmet need for more effective treatments for patients with small cell lung cancer (SCLC), a highly lethal malignancy with an incidence rate similar to that of ovarian cancer or glioblastoma. Recently we discovered that poly (ADP-ribose) polymerase 1 (PARP1), a protein that repairs damaged DNA, is dramatically overexpressed in SCLC and that SCLC cells are killed by treatment with drugs that inhibit PARP1. We predict that PARP inhibition may increase the activity of chemotherapies that act by damaging the DNA of cancer cells. Therefore, we designed a clinical trial to test the combination of a PARP inhibitor (ABT-888) with chemotherapy (TMZ) in SCLC  patients who have progressed despite receiving one or more standard chemotherapy regimens. In this project, we will develop potential tumor and blood biomarkers that can predict those patients most likely to benefit from this therapy. Our results are directly applicable to the clinic and will lead to more personalized therapeutic strategies for proteins battling this deadly disease. Preliminary data garnered through these studies will be invaluable for future planned clinical trials of PARP inhibitors in SCLC and potentially in other malignancies, such as breast and ovarian cancer, where these drugs have shown clinical activity.