GRANTEE: Kazuki Sugahara, MD, PhD
Co-PI: Andrew Lowy, MD, FACS, University of California, San Diego
Research Project: Clinical development of a tumor-penetrating peptide for enhanced pancreatic cancer therapy
Award: 2015 Pancreatic Cancer Action Network Translational Research Grant
Award Period: July 1, 2015 – June 30, 2017
Dr. Sugahara is an adjunct associate research scientist in the department of surgery at Columbia University College of Physicians and Surgeons, and an adjunct assistant professor at the Cancer Center, Sanford-Burnham Medical Research Institute in La Jolla, Calif. Dr. Sugahara was awarded a Career Development Award from the Pancreatic Cancer Action Network in 2012, generously funded by The Daniel and Janet Mordecai Family Foundation.
Dr. Lowy is professor of surgery and chief, division of surgical oncology at UC San Diego Moores Cancer Center. Dr. Lowy serves as the co-chair of the National Cancer Institute Pancreatic Cancer Task Force that advises the Gastrointestinal Cancers Steering Committee on clinical trials planning.
One of the challenges to effectively treating pancreatic cancer is ensuring that drugs are actually delivered to and within the tumor. Pancreatic tumors are known to be surrounded and infiltrated by dense tissue, known as the stroma, which is thought to impede drug delivery.
Drs. Sugahara and Lowy and their research teams have devised a strategy to circumvent the issue of drug delivery. The team has developed a peptide, a small piece of a protein, which is able to penetrate the stroma and localize within the tumor. If a drug is administered in combination with this peptide, known as iRGD, the drug also penetrates the tumor and kills the cancer cells. Moreover, early experiments in mice genetically programmed to develop pancreatic tumors have suggested that iRGD administered alone can itself inhibit metastasis, or spread, of the cancer cells.
The goal of this research project is to accumulate the necessary preclinical data to allow iRGD to get Investigational New Drug (IND) status from the Food and Drug Administration. Then, iRGD will be able to be tested in early-phase clinical trials in pancreatic cancer patients. In order to file for IND status, the team of collaborators will examine whether iRGD enhances the anti-cancer activity of gemcitabine plus nab-paclitaxel, a common treatment regimen for pancreatic cancer patients, in mice. Next, they will investigate potential side effects and determine the optimal dosing for iRGD in combination with gemcitabine and nab-paclitaxel in the genetically engineered mice. The research team envisions iRGD-based therapy in the context of enhancing chemotherapy administered prior to surgery for locally advanced disease, targeting recurrence after surgery and controlling metastasis.