Promising Trial at Columbia Explores Novel Treatment for Diffuse Gastric Cancer
The rise in early-onset cancers, those diagnosed before age 50, has become increasingly concerning, especially in digestive system cancers such as stomach cancer and colorectal cancer. Early-onset esophagogastric cancer (EOEGC), a rare but aggressive cancer that affects the esophagus and stomach, has seen a 30% increase in incidence over the past several decades and accounts for approximately 10-15% of new cases. This disease differs from traditional esophagus and stomach cancers, often occurring in younger individuals and progressing rapidly, making early diagnosis and effective treatment critical.
Ryan Moy, MD, PhD, assistant professor of medicine and a medical oncologist at Columbia University Irving Medical Center, is pioneering research in characterizing the unique molecular features of EOEGC along with collaborator Lawrence Wu, MD, a clinical fellow in the division of hematology/oncology. Findings from their research, presented by Wu at the 2024 American Association for Cancer Research (AACR) Annual Meeting, highlight distinct genetic and molecular characteristics of EOEGC that could pave the way for more targeted treatments in the future. They are also researching potential racial, ethnic, and gender disparities that exist in EOEGC.
Moy, a member of the Cancer Genomics and Epigenomics program at the Herbert Irving Comprehensive Cancer Center (HICCC), is also the principal investigator of a new clinical trial at Columbia aimed at tackling diffuse gastric cancer (DGC), an especially aggressive subtype of stomach cancer that is resistant to many of the standard treatments available today. Diffuse gastric cancer often spreads to the abdominal lining, resulting in painful fluid buildup that requires frequent drainage, making it one of the most challenging forms of gastric cancer to manage. Although recent advances in immunotherapy have improved outcomes for some stomach cancer patients, DGC’s distinct characteristics make it less responsive to these newer therapies.
The Columbia-led trial seeks to address this gap by using a promising combination of drugs called kinase inhibitors, which work to stop cancer by targeting specific enzymes needed for cell growth. Defactinib and avutometinib, both pill-based therapies, block the focal adhesion kinase and mitogen-activated protein kinase pathways, which play critical roles in the growth and spread of DGC.
The drug combination tested at Columbia has shown efficacy in laboratory models of DGC and has also been safe and well-tolerated in patients with other cancers, including ovarian and lung cancers. Unlike traditional chemotherapy, which requires frequent hospital visits and can be taxing for patients, this pill-based treatment allows for more flexibility, potentially improving patients’ quality of life while they undergo treatment.
“We hope to transform treatment for DGC by providing a more targeted, accessible option for patients facing this difficult diagnosis, with the added potential of identifying biomarkers that could lead to further personalized approaches,” says Moy.
