UNC Lineberger’s Channing Der, PhD, Sarah Graham Kenan Distinguished Professor in the UNC School of Medicine Department of Pharmacology, was co-corresponding author of a paper published in Cancer Discovery. Antje Schaefer, PhD, research assistant professor in the UNC School of Medicine Department of Pharmacology, was co-first author.

UNC Lineberger's Channing Der, PhD, and Antje Schaefer, PhD.
UNC Lineberger’s Channing Der, PhD, and Antje Schaefer, PhD.

In the study, researchers identified a new potential drug target in stomach cancer with two key mutations.

One of the previously known common mutations in diffuse gastric cancer is a mutation in a tumor suppressor gene called CDH1. In mouse models, researchers investigated how cancer develops as a result of mutations in Cdh1 and in another in a gene called Rhoa, or RAS homologous small GTPase. The RHOA mutation was more recently discovered in gastric cancer.

They detailed the impact of a specific type of Rhoa mutation, and found that that combination of this mutation and loss of the Cdhi tumor suppressor causes metastatic diffuse gastric cancer in mice resembling human disease. They further characterized the impact of these mutations within cancer cells, and identified a potential therapeutic approach for the treatment of Rhoa-mutant gastric cancers.