INDIANAPOLIS--Two researchers at the Indiana University Melvin and Bren Simon Comprehensive Cancer Center have received a five-year, $2.4 million grant from the National Cancer Institute (NCI) to explore new therapies that target the critical pathways pancreatic tumors use to survive.
The highly competitive NCI award will allow Mark Kelley, PhD and Melissa Fishel, PhD, both of the Herman B Wells Center for Pediatric Research and the IU School of Medicine Department of Pediatrics, to build on specific advances they’ve made in their adjacent labs and as part of the cancer center’s Pancreatic Cancer Challenges and Solutions Working Group, of which Fishel is a co-leader.
The two have collaborated for more than 20 years and developed drugs and therapies now used to treat people with pancreatic cancer. Though these patients are living longer after their diagnosis, the disease still has a five-year survival rate of just 12 percent.
Research targets Ref-1
Kelley has been building on research in this area for more than three decades.
“Cancer is an accumulation of errors. So it follows that an effective way to arrest cancer … [is] to block a pathway by which cancer sustains itself,” Kelley wrote in the journal Current Molecular Pharmacology earlier in his career. He was writing even then about a protein called Redox factor-1 (referred to as Ref-1) function—a protein that can promote signaling in cancer and its progression, especially cancer that starts in the pancreas.
“Our earlier research advanced a first-generation Ref-1 inhibitor, the drug APX3330, to a Phase I clinical trial in adult cancer patients. That work allowed us to identify the next generation of Ref-1 inhibitors, along with a strategy for identifying patients with a sensitivity to Ref-1 inhibition and drugs likely to make our Ref-1 inhibitors work better,” Kelley said in response to this new grant. “Now, with this grant, we propose to investigate Ref-1 alone and in combined therapies that we believe will better inhibit pancreatic cancer growth and metastasis by infringing on the critical pathways tumors use to survive.”
The research has two specific aims:
1. Identify the characteristics of cells that respond to Ref-1 inhibition to predict new therapy combinations.
2. Evaluate how well combination therapies overcome a cancer cell’s resistance and move the best therapies toward clinical trials.
Kelley is associate director of basic science at the cancer center and co-leader of the cancer center’s Cancer Drug Discovery and Development Accelerator.
Fishel co-leads the cancer center’s Tumor Microenvironment and Metastasis research program and a project in the National Institutes of Health/National Cancer Institute Pancreatic Ductal Adenocarcinoma Stromal Reprogramming U01 Consortium, for which she recently received a new grant.
Learn more about the cancer center’s pancreatic cancer initiatives.
About the IU Simon Comprehensive Cancer Center
The Indiana University Melvin and Bren Simon Comprehensive Cancer Center is the state’s only National Cancer Institute-designated Comprehensive Cancer Center and one of only 56 in the nation. The prestigious comprehensive designation recognizes the center’s excellence in basic, clinical, and population research, outstanding educational activities, and effective community outreach program across the state. It is also one of only 33 members of the National Comprehensive Cancer Network. As a member, the center’s physicians have a role in determining the recognized standard of clinical care for cancer patients. The center is the central hub for cancer research and education across Indiana University.