A University of Houston researcher has developed a synthetic compound, MA242, that can inhibit two of the major pathways of highly aggressive pancreatic cancer.
Ruiwen Zhang, a Robert L. Boblitt Endowed Professor in Drug Discovery, has published his findings, along with research associate professor of pharmacology Wei Wang, in Cancer Research Journal.
The drug may be a first-in-class, new therapy for pancreatic cancer and a new conceptual framework for developing other drugs.
“We developed a synthetic compound that we call MA242, and it can deplete both proteins at the same time increasing specificity and efficiency of tumor killing,” said Zhang. “In our molecular modeling study, MA242 is a potent dual inhibitor.” Though man-made, the new compound is based on a type of sea sponge.
Stromal depletion and immunotherapy also have been proposed to offer substantial promise for treating advanced pancreatic cancer, but their therapeutic impact remains unclear.
The two cancer-causing genes linked in pancreatic cancer are nuclear factor of activated T cells 1 and murine double minute 2, a gene that regulates, and depletes, the tumor suppressor gene called p53. If there is no tumor suppressor p53 present, MDM2 will cause cancer on its own. NFAT1 up-regulates MDM2 expression and encourages tumor growth.
Patients with pancreatic cancer have too much MDM2 and NFAT1, which has left these genes as open targets for cancer therapy. Numerous studies have shown reduced MDM2 can lead to decreased tumor growth and progression. Healthy individuals have low levels of MDM2 and NFAT1, but diet, nutrition and environment can cause higher levels in cells, said Zhang.
