Samuel J. Klempner, M.D., was completing his fellowship at Beth Israel Deaconess Medical Center in Boston when he first became interested in studying the process by which gastric cancer spreads to the peritoneum—the membrane that lines the abdominal cavity. Now he’ll be able to take a major step towards solving that mystery, having recently been chosen as the recipient of a $300,000 research grant from the Gastric Cancer Foundation and the American Gastroenterology Association (AGA).

“One of the biggest knowledge gaps in gastric cancer is the peritoneum,” says Klempner, a gastrointestinal medical oncologist and assistant professor at Harvard Medical School and Massachusetts General Hospital. “This funding will allow us to generate preliminary data and take it to the next step,” potentially identifying new therapeutic vulnerabilities to exploit in the mission to help improve the prognosis for patients with metastatic gastric cancer.

The AGA–Gastric Cancer Foundation Ben Feinstein Memorial Research Scholar Award in Gastric Cancer provides $100,000 per year for three years to young scientists working towards careers in gastric and esophageal cancer research. Klempner is the third recipient of the award.

Klempner’s research focuses on studying the composition of the fluid that accumulates in the abdomens of gastric cancer patients with peritoneal spread. This fluid, called ascites (uh-SY-tees), contains some gastric cancer cells, but figuring out what else is in the mix could greatly advance the search for new treatments, Klempner believes.

“What’s in ascites is essentially a black box,” he says. “We don’t know the immune cell composition or secreted factors that are there. We don’t even know much about the tumor cells that are in there. So part one of the project is to get a baseline understanding of that, which could inform rational approaches to treatment for this underserved population.”

Klempner’s team has been building a biobank of ascites and blood samples collected from gastric cancer patients before they receive any drug therapies to treat their cancer. “We want to understand the landscape at diagnosis,” he explains. The plan is to take additional samples from the same patients during their treatment regimens. “That will help us understand how the cells of the ascites are adapting and responding to the pressures of treatment.”

The second phase of the research will focus on characterizing immune components of the ascites, including “checkpoints,” which are proteins that prevent the immune system from recognizing and attacking cancer. Klempner hopes the results will ultimately lead to clinical trials of new combinations of immune-boosting drugs.

Klempner, a graduate of the University of Massachusetts Medical School, grew up on a farm in Wayland, MA, and now lives with his wife in Boston. As a lifelong sports lover, he’s naturally drawn to problems that require teamwork to solve—and gastric cancer is a perfect fit, he says. “You have your nutritionists, your surgeons, gastroenterologists, radiation oncologists, radiologists and pathologists. You can’t take care of stomach cancer patients on your own.”

Now thanks to the new grant, the Gastric Cancer Foundation is a vital member of his team, Klempner says. “This is a sizeable award that will lay the foundation for us to hopefully take this research in multiple future directions.”

Dr. Saenz, with the Division of Gastroenterology at Washington University School of Medicine, is the second Research Scholar for gastric cancer – awarded in May 2017. Dr. Saenz is studying how the bacterium Helicobacter pylori, the greatest risk factor for developing gastric cancer, adapts to the stomach environment.

An Interview with Dr. Saenz:

How did you become interested in gastric cancer research?

It was a perfect way for me to marry my background in microbiology and explore new avenues in cancer research.  Infection with the gastric bacterium Helicobacter pylori is the greatest risk factor for developing gastric cancer. I am fascinated by the ability of a bacterium to live for decades in an inhospitable environment like the stomach, all the while changing the gastric landscape to survive and lead to cancer in the process.  

How will the AGA-GCF Research Scholar Award in Gastric Cancer help your research over the next three years?

If we can begin to understand how Helicobacter pylori genetically adapts to different regions of the stomach, this may clue us to which bacterial genes are important for survival in these regions, and we can begin to target these genes therapeutically.  We can also use these bacterial genes as biomarkers so that we can identify people infected with bacterial strains that harbor these genes.  Then we will be able to detect patients with an increased risk based on the bacterial profiles.

How does this AGA-GCF support help young scientists in the gastric cancer field?

I trust my research will help other scientists learn more about the microbial-host interactions that dictate the development of gastric cancer.  The hope is that this research will inspire other scientists in the field to look at the interactions early in infection as being crucial events that might create a micro-environment that can progress to cancer.

What is your hope for your current research?

Ultimately, I would like to see my research lend insight into better understanding how Helicobacter pylori adapt to the stomach environment.  We need to fundamentally explore these early interactions if we want to be able to identify high-risk patients and improve gastric cancer mortality, which is unacceptably high in the United States—and worldwide.

The first recipient was Mohamad El-Zaatari, Ph.D., from the University of Michigan, developed three different research proposals as result of the Foundation’s seed funding.  His investigations focused on studying how chronic inflammation causes certain cells to become malignant and changes in inflamed stomach tissue that lead to precancerous conditions. With the help of the Foundation’s initial funding, Dr. El-Zaatari has now received Congressional medical research funding through the Department of Defense to continue his breakthrough research on “Targeting B Cell-Mediated Type II Autoimmunity in Gastric Carcinogenesis.”

 “This grant has enabled me to pursue research and show substantial results so I can seek larger grants to continue these important studies. With grants like this one, the Foundation has the ability to develop an army of investigators to pursue research on this scarcely funded cancer.”  2016