Seed Grant Recipient Pinpoints Four Promising Treatment Candidates for Gastric Cancer
For Gastric Cancer Foundation grant recipient Dr. Kishore Guda, one big benefit of early-stage research funding from private foundations is that it offers the freedom to pivot when initial hypotheses don’t pan out as expected. That’s what happened to Guda and his team at the Digestive Health Research Institute of Case Western Reserve’s School of Medicine, where he is an associate professor.
Guda’s pivot turned out to be a productive one. Initially, his plan for the $100,000 grant he received from the foundation in 2023 was to investigate the potential of vactosertib, a drug that targets a protein called transforming growth factor beta (TGF-β), in treating gastric cancer. The drug had shown some promise in esophageal cancer, but Guda’s initial studies demonstrated that it wasn’t as effective in preclinical models of gastric cancer.
So Guda’s team decided to see if they could find something better. They started with a list of about 3,000 compounds that are currently in clinical trials or approved to treat other diseases. After testing them in gastric cancer cells and organoids—tiny, live models of the stomach—they found 10 compounds that showed efficacy against the disease. Further testing in mouse models helped them narrow the list to four drug candidates.
One notable commonality among the selected compounds is that they show “differential sensitivity,” meaning some subsets of gastric cancer cells respond to them while others don’t.
This will help us understand the mechanism of how each drug works, and it will enable us to identify biomarkers that may help in the future to select patients most likely to respond.
– Dr. Kishore Guda
Guda’s plan is to further test the four candidate compounds in animal models, with the eventual goal of assembling a framework for early-phase human trials.
This research is part of a large and diverse portfolio of projects that Guda and his research team are pursuing. Earlier this year, he and his colleagues discovered a specific type of long intergenic non-coding RNA (lincRNA) called lincPKRD, which appears to be active in both esophageal and gastric cancer. The study, published in Gastro Hep Advances, could point to novel and personalized therapies for patients with the disease, Guda said.
As he continues to pursue novel approaches to combating gastric cancer, Dr. Guda said, he is grateful for GCF’s support. “Private foundations like GCF play a key role. The funding allows us to answer pressing questions very quickly and then go a different route if we need to,” he said. “That’s critical for speeding up discoveries that will eventually benefit patients.”
