AACR-Bayer Innovation and Discovery Grants
The AACR-Bayer Innovation and Discovery Grants represent a joint effort to promote the key tenets of the Bayer Grants4Targets™ Initiative, providing new treatment options for cancers with high unmet medical need, encouraging innovation and translation of ideas from basic research into novel drugs, and fostering collaborations between academic groups and the pharmaceutical industry.
Although mutant KRAS can be silenced in vitro by RNAi, attempts to target KRAS in vivo have been met with obstacles and, therefore, this oncogene has been labeled as “untargetable.” The cholecystokinin-B receptor (CCK-BR) is not found in normal pancreas but becomes overexpressed in precancerous PanIN lesions and in pancreatic cancer. Dr. Smith’s group has developed a biodegradable fluorescent polyplex nanoparticle that selectively targets the CCK-BR that can carry a siRNA payload to inhibit growth of human pancreatic cancer in mice. In this project, fluorescent CCK-BR targeted nanoparticles will be used to deliver mutant KRAS siRNA to high grade PanINs using the mutant Kras (LSL-KrasG12D/+;P48-Cre) mouse model in order to prevent PanIN progression. In addition, the KRAS siRNA loaded nanoparticles will be used to treat orthotopic established pancreatic cancer in immune competent mice.
Dr. Smith is a professor of medicine at the Lombardi Comprehensive Cancer Center at Georgetown University. Dr. Smith also practices at the Washington DC Veterans Affairs Medical Center. As a clinical scientist, Dr. Smith has dedicated her entire academic career to patient care, teaching, and conducting research. Her passion has been bench-to-bedside translational research. Her basic science research has focused on G-protein-coupled receptors, in particular cholecystokinin receptors and their role in gastrointestinal cancers.
Acknowledgment of Support
The outcome of our work could lead to a new approach for targeting KRAS in pancreatic cancer. This fluorescent target-specific nanoparticle, or theranostic agent, can be developed for both treatment (therapy) and early detection (diagnosis) of high grade PanIN-3 lesions in order to prevent pancreatic cancer. We would like to acknowledge support for this project from the 2021 AACR-Bayer Innovation and Discovery Grant.