Grant Helps Researchers Study Pancreatic Cancer Treatment in Phase I Trials

A team at the UC Cancer Institute will continue studies on a combination pancreatic cancer therapy with recent support from GIVEHOPE.

The grant, totaling $47,500, will help researchers further study the coupling of chemotherapy with a biologically targeted therapy for the treatment of pancreatic cancer.

Olugbenga Olowokure, MD, associate professor, Xiaoyang Qi, PhD, professor, and John Morris, MD, professor, all in the Division of Hematology Oncology at the UC College of Medicine and members of the Cincinnati Cancer Center and UC Cancer Institute, will be leading the study.

"Pancreatic cancer remains one of the most difficult of all cancers to treat, with poor outcomes and relatively short survival rates for patients,” says Olowokure. "Over 90 percent of pancreatic cancers are ductal adenocarcinomas—meaning the cancer develops from cells lining small ducts in the pancreas. In the U.S. in 2017, it is estimated that over 53,000 people will be diagnosed with pancreatic cancer and approximately 43,000 people will die of pancreatic cancer. At the time of diagnosis, over 50 percent of patients will have metastatic disease, despite accounting for about 3 percent of malignancies. In total, this disease remains the fourth leading cancer-related cause of death in both men and women.

"Currently there are very few effective treatment options for patients with advanced metastatic disease, and outside the setting of a clinical trial, the two main regimens considered for patients are two chemotherapy combinations: gemcitabine plus Nab-paclitaxel or FOLFIRINOX, an additional chemotherapy combination used for pancreatic cancer. The FDA approved Nab-paclitaxel in combination with gemcitabine for first-line treatment of patients with metastatic adenocarcinoma of the pancreas in 2013.”

Qi discovered that SapC-DOPS, the combination of a lysosomal protein saposin C (SapC), and a phospholipid, known as dioleoylphosphatidylserine (DOPS), that when assembled into tiny cavities, or nanovesicles, can target and kill many types of cancer cells. He did this while working at Cincinnati Children’s in the 1990s and continues his research at UC.

Lysosomes are membrane-enclosed cellular organelles that contain enzymes capable of breaking down all types of biological components; phospholipids are major components of all cell membranes and form lipid bilayers—or cell membranes.

Qi says his lab found that the combination of these two natural cellular components, or SapC-DOPS, caused cell death in various human cancer cell types, including brain, lung, skin, prostate, blood, breast and pancreatic cancer, while sparing normal cells and tissues in animal models of human cancer.

The clinical equivalent of SapC-DOPS, known as BXQ-350 sponsored by Bexion Pharmaceuticals, is now being studied in clinical trials.

"SapC-DOPS has shown strong inhibitory impact on pancreatic cancer cells regardless of their genetic modifications,” Qi adds. "Also, no major toxicities were observed in a preclinical safety investigation.”

Additionally, combination treatment of gemcitabine with SapC-DOPS showed improvement in cancer progression.

"Preclinical studies of SapC-DOPS as a novel anticancer agent demonstrate a toxicology and pharmacology profile that favors advancement to early-phase clinical trials,” says Olowokure. "In this study, we will use BXQ-350 combined with Nab-paclitaxel and gemcitabine as a chemotherapeutic combination for patients with metastatic pancreatic cancer.”

This will be carried out in a Phase I clinical trial to test for the appropriate dosage and safety of the treatment. Morris is the director of the Phase I/Experimental Therapeutics Program within the UC Cancer Institute. This is the only program of its kind locally.

"Our hope is to find a new effective therapy for pancreatic cancer that will also reduce side effects for patients,” says Olowokure. "We’re thankful to GIVEHOPE for continuing to support our work with hopes of finding new and better treatments for this illness.”