Development of drug for the treatment of Hereditary Diffuse Gastric Cancer (HDGC)

Through a grant funded by No Stomach For Cancer, principal investigators Lyvianne Decourtye-Espiard and Parry Guilford from the Centre for Translational Cancer Research, University of Otago, Dunedin, New Zealand, have identified the drug Entinostat as a promising candidate for the chemoprevention of Hereditary Diffuse Gastric Cancer. “We have tested it in various human cell lines (with and without CDH1 mutations) and 3D cell populations derived from mouse stomachs and mammary tissue (‘organoids’). In each case, the cells/organoids with the CDH1 mutation showed greater sensitivity to the drug. We now plan to test Entinostat in more genetically complex organoid models and a new mouse model of diffuse gastric cancer that we have recently developed. We will also try it in combination with other potential chemoprevention drugs that have been identified in our laboratory. Synergistic combinations can reduce the amount of medicine given to patients, reducing the severity of drug side effects.”

If Entinostat performs well in the mouse studies, the next step will be to validate the drug in CDH1 mutation carriers as part of a clinical trial. This research on Entinostat is part of a broader program of work being carried out by the laboratory that currently involves approximately nine promising candidate drugs for the chemoprevention of Hereditary Diffuse Gastric Cancer (HDGC). Their research also investigates novel drug delivery systems that may enable them to deliver medications directly to the stomach tissue (perhaps annually at the time of routine surveillance endoscopy), minimizing the risk of treatment side effects.

About University of Otago Centre for Translational Cancer Research
Leading cell biologists, immunologists, medicinal chemists, oncologists, and surgeons collaborating to address very specific clinical needs in cancer research. The Centre was established in 2007 with the goal to improve the survival and quality of life of cancer patients. By responding to needs and weaknesses in cancer care, as identified by clinicians and patients, they are bringing new and more effective options for diagnosing and treating cancer.