Studies examine anti-cancer compound developed at Mitchell Cancer Institute

By Carol McPhail

CMcPhail@health.southalabama.edu

USA Health cancer researchers are trying to unravel a mystery that has perplexed oncologists and their patients for decades – how to stop cancer in its tracks.

An anti-cancer compound developed at USA Health Mitchell Cancer Institute is showing promise in pre-clinical studies – one involving pancreatic cancer and the other involving breast cancer. The compound, MCI-715, was developed by Gary Piazza, Ph.D., and his lab team at the Drug Discovery Research Center at MCI.

“MCI-715 was designed to inhibit the activity of a specific protein overexpressed in cancer cells that drives malignant progression, as well as resistance of cancer cells to conventional chemotherapeutic drugs,” said Piazza, professor of pharmacology at the University of South Alabama College of Medicine.

The pre-clinical studies were conducted in Australia and Alabama.

Researchers at Curtin University in Western Australia studied MCI-715’s effectiveness against pancreatic ductal adenocarcinoma (PDAC), a highly aggressive cancer for which chemotherapeutic drugs provide limited benefits and are associated with severe toxicities.

“We were able to show that by targeting this specific protein with the modified drug, it significantly decreased the spread of PDAC and slowed tumor growth,” said Marco Falasca, Ph.D., professor at the School of Pharmacy and Biomedical Sciences at Curtin University. Falasca was lead author of an article on the research published in the Journal of Experimental and Clinical Cancer Research.

Falasca said the findings have potential implications for human clinical trials because the pancreatic cancer protein being targeted is known to be resistant to chemotherapy. “Any discovery that can improve the survival rates of patients with pancreatic cancer and provide another treatment option is significant,” he said.

Meanwhile, University of Alabama at Birmingham researcher Clinton Grubbs, Ph.D., found that MCI-715 was effective in a pre-clinical model of breast cancer prevention to a level comparable to tamoxifen. Tamoxifen is widely used to prevent the progression of breast cancer in high-risk patients but is also associated with severe side effects.

“Based on these data, a second study is planned to further evaluate efficacy and toxicity in a more comprehensive manner,” said Grubbs, director of the Chemoprevention Center in the UAB Department of Surgery. The Breast Cancer Research Foundation of Alabama supports a joint grant that funds Grubbs’ and Piazza’s research.

Piazza said the results from the two independent labs, along with studies at MCI, provide “compelling evidence that MCI-715 has promising anti-cancer activity.”

“These results support the need for further pre-clinical studies to further assess the efficacy and safety for the prevention or treatment of cancers,” Piazza said.