2023 LCRF Research Grant on Understanding Resistance in Lung Cancer
Ann Pendergast, PhD
Duke University School of Medicine
Research Project:
Uncovering novel vulnerabilities to treat SCLC therapy resistance
Summary:
Small cell lung cancer (SCLC) is a highly aggressive neuroendocrine lung cancer that is typically metastatic upon diagnosis. The overall 5-year survival rate for SCLC patients is only ~7%, and has remained unchanged for over 30 years. Therefore, there is an urgent need to define the molecular mechanisms that promote metastatic SCLC in order to identify effective treatment strategies to treat this deadly cancer. The Pendergast laboratory recently found that pharmacologic inhibition of ABL kinases with ABL-specific inhibitors impairs SCLC metastasis in mouse models, resulting in prolonged animal survival. This proposal will evaluate whether ABL kinase inhibition sensitizes SCLC to therapies targeting stress response pathways, and/or to metabolic inhibitors.
1-year update: spring 2025
What she’s doing:
Dr. Pendergast is conducting groundbreaking work to uncover new ways to treat therapy-resistant small cell lung cancer (SCLC). Her research focuses on understanding how cancer cells communicate at the molecular level, specifically through RNA messages.
How it’s going:
Dr. Pendergast’s team has identified ABL, a proto-oncogene that supports cancer growth, as a key target. By inhibiting ABL, they’ve found that cancer cells experience increased DNA damage, which can slow or stop tumor growth. Even more promising, when combined with ATR inhibitors—a protein that protects cells from DNA damage—this approach significantly reduced metastatic tumors and prolonged survival in tumor-bearing mice.
What it could mean for patients:
While this research is still in its early stages, discoveries like these lay the foundation for smarter, more effective therapies for patients with SCLC.