Unexpected Research Pivot Leads Seed Grant Recipient to New Gastric Cancer Targets
When Dr. Ryan Moy first received a $100,000 seed grant from Gastric Cancer Foundation in 2023, his goal was to investigate the potential of a novel cell therapy targeting CLDN18.2, a protein that’s expressed at high levels in about one-third of gastric cancers. But the company that had planned to provide the cells Moy and his research colleagues needed to do the study was unable to fulfill its commitment, so they revised their plan.
They decided instead to investigate a pathway called YAP/TEAD, which is known to drive the growth of gastric cancer cells. They wanted to determine whether targeting both YAP/TEAD and CLDN18.2 could improve upon therapies that target CLDN18.2 alone. It was a timely pursuit: The first CLDN18.2-targeted drug, Vyloy (zolbetuximab) was approved to treat HER2-negative gastric cancer in October of 2024.
Moy, Assistant Professor of Medicine and medical oncologist at Columbia University’s Irving Medical Center, and his team completed studies showing that inhibiting TEAD1 reduced stomach cancer growth in mouse models of gastric cancer and cellular models derived from patients. They were also able to characterize different levels of CLDN18, TEAD1 and pYAP in different gastric cancer cell lines. They are now planning to test zolbetuximab in those cell lines to further understand its effects on YAP/TEAD.
The work done with Gastric Cancer Foundation’s seed grant “provided some future directions to look at how targeting this pathway might improve CLDN18.2-directed therapies,” Moy said. “Zolbetuximab has some side effects that can make it difficult for some patients to tolerate. Finding other strategies that that might help improve its activity while reducing some of the side effects would be helpful.”
In addition to participating in preclinical research, Dr. Moy develops and leads clinical trials investigating novel treatments for esophagogastric cancer, including trials in people who develop the disease before the age of 50. In 2024, research he led characterizing molecular features of this “early-onset” esophagogastric cancer was featured at the prestigious American Association for Cancer Research (AACR) Annual Meeting.
He’s enthusiastic about continuing his research on the YAP/TEAD pathway in gastric cancer. He noted that there are ongoing clinical trials of drugs that inhibit TEAD, which could pave the way to future trials of combination treatments.
“I’m incredibly grateful to Gastric Cancer Foundation for providing funding for this work. Particularly now, with decreased federal funding available for cancer research, this help from organizations like the foundation can really help speed along progress in finding new gastric cancer treatments.”
