Foundation Grant Winners Report Progress in Research Aimed at Combating Gastric Cancer
In 2021, the Gastric Cancer Foundation awarded two $100,000 grants to researchers pursuing novel approaches to treating gastric cancer, as part of our goal of supporting scientists who have promising but unproven ideas. We’re excited to report that the funding helped generate data that both grantees said will be vital to moving the research forward.
The grants were awarded to Timothy Wang, M.D., professor at Columbia University Vagelos College of Physicians and Surgeons, who is focused on improving immunotherapy in gastric cancer, and Nina Salama, Ph.D., professor at Fred Hutchinson Cancer Research Center, who studies the role of bacterial infections in the disease.
Wang’s research is focused on myeloid derived suppressor cells (MDSCs), immature cells that suppress the immune system’s T cells, which are critical for mounting an attack against cancer. MDSCs reduce the effectiveness of drugs that inhibit the immune checkpoint PD-1. Wang’s lab used the grant to develop two new mouse models of gastric cancer, and to test a combination in one of them that includes an anti-PD-1 drug and a novel protein called TFF2-CTP. They found that in the mice, the treatment decreased MDSCs and increased the population of cancer-fighting CD8-positive T cells by 50-fold.
Wang will present data from his research in a poster that was accepted for the annual American Association for Cancer Research (AACR) in April. He is also working with Tonix Pharmaceuticals to develop TFF2-based therapies for clinical trials in patients with gastric and colorectal cancers.
“[The Foundation’s funding] allowed me to move in a therapeutic direction to something that could have promise for patients,” Wang said. “I wouldn’t have gotten this far down the road had it not been for the grant.”
Salama’s lab recently began studying the role of the mouth bacterium Fusobacterium nucleatum in gastric cancer and how it differs from that of the better-known stomach bacterium Helicobacter pylori. The Foundation’s grant allowed Salama and her colleagues to build “organoids,” which are models of gastric cancer built from human or mouse stomach tissue. They are using mouse organoids of normal stomach tissue and of metaplasia—a precancerous condition that’s associated with an increased risk of gastric cancer—to study how H. pylori and F. nucleatum interact with stomach tissue.
In one study, Salama’s lab identified two types of gene expression that H. pylori induces in both mouse and human gastric cells, putting them on a path to metaplasia. F. nucleatum does not have the same effect, even though it also has been associated with gastric cancer, they found. They also discovered that treating the models with steroid that blocks inflammation reduced the expression of the two genes, even in the presence of the bacteria.
Salama says the work fueled by the Gastric Cancer Foundation grant complements a $275,000 two-year grant she later received from the National Institutes of Health (NIH) to study the role of H. pylori and F. nucleatum in gastric cancer development. The organoids developed with the Foundation’s grant “allowed us to jumpstart experiments. We can hit the ground running with this NIH grant and really use it to look at how common drivers in gastric cancer affect tissues exposed to each of these bacteria.”
She adds that seed funding provided by the Foundation is crucial for fueling novel approaches to gastric cancer.
“I can’t emphasize enough how appreciative my team is to get this support,” she says. “We’re developing tools that are really enabling us to carry this basic research on how bacteria can drive cancer forward.”