Taking Aim at Stomach Cancer Locally…and Globally

Principal Investigator Joo Ha Hwang, MD, PhD, specializes in early detection of gastrointestinal malignancies. 

December 11, 2023 - by John Knox

Stomach cancer, the fourth leading cause of cancer deaths worldwide, has received far less attention in the United States than many other malignancies. But a team of physician scientists from Stanford aims to change that with the support of the National Cancer Institute (NCI).

In September 2023, the NCI awarded $9.15 million to Principal Investigators Joo Ha Hwang, MD, PhD, and Hanlee Ji, MD, who are part of a multi-disciplinary team working on a five-year project to study “Precision Interception of Gastric Cancer Precursors Through Molecular and Cellular Risk Stratification.”

“This is only one of two program project grants awarded by the National Institutes of Health for the study of gastric cancer,” says Hwang, professor of Gastroenterology and Hepatology.

“This newfound attention to improving the early detection and treatment of gastric cancer in the U.S. has ramifications for the rest of the world. Although there is significant research in South Korea, Japan, China, and some other nations, having the U.S. engage more on this problem will have a major impact globally because most of our research efforts here send ripples throughout the world,” says Ji, professor of Oncology.

A hallmark feature of gastric cancer in the United States is late diagnosis; fewer than three in ten gastric cancers are diagnosed at a curable stage, so outcomes from the disease are exceedingly poor, with five-year survival less than 35%.  Individuals with gastric intestinal metaplasia (GIM), a precancerous stomach lesion, are at much greater risk for subsequent gastric cancer. Therefore, early detection of GIM offers a promising opportunity for intercepting cancer. 

Professor of oncology, Hanlee Ji, MD, is also primary investigator on this new NIH gastric cancer study. 

Team Science

The basis for the NCI-funded project began with Hwang and Robert Huang, MD, instructor of Gastroenterology and Hepatology. They wanted to identify patients most at risk for stomach cancer. Aware that early lesions like GIM can lead to cancer, several years ago the two gastroenterologists started developing a gastric registry to gather data about these early cancer precursors from patients across the Stanford catchment area.

In 2020 they began partnering with Ji, whose research group in the Division of Oncology was developing its own gastric cancer registry. That registry, which amassed case data from throughout the U.S. and other spots around the world, included a significant genetic and molecular genomic analysis component. Together, the three began applying molecular analyses to the precursor lesions found in cancer stomach patients to determine with more precision what molecular features define someone at very high risk for developing stomach cancer.

Next, Hwang, Huang, and Ji sought the expertise of Summer Han, PhD, a statistician and epidemiologist skilled at looking at biomarkers and considering their risk factors to help detect patients who might be at risk for developing cancer. Han is associate professor of Biomedical Informatics Research.

Understanding that the microbe Helicobacter pylori, or H. pylori, increases the risk of gastric cancer and is one of the leading risk factors found internationally, the four researchers engaged Manuel Amieva, MD, professor of Pediatrics-Infectious Diseases, who had a longstanding interest in H. pylori. Amieva’s participation rounded out the team with his contributing cellular biology expertise to the project.

If they can find the molecular features that are common to patients who will eventually develop gastric cancer, then they can use those features to say if a patient is at high risk for the disease. That patient can then be placed under surveillance with endoscopy more frequently than someone else whose risk is determined to be relatively low.

Research Goals

“Our project is focused on trying to find key features of those early lesions that would suggest they are at very high risk to go on to developing cancer. We will be looking at ways of potentially detecting patients who are at higher risk and monitoring them more carefully, versus those who don't need as careful monitoring. Given limited diagnostic resources, this molecular-driven approach has the potential to improve the effectiveness of screening while lowering the cost,” says Ji.

The team’s studies are expected to reveal more about what differentiates a normal healthy stomach cell from a cancerous stomach cell.

“When we understand what starts a normal stomach cell moving on its way to becoming cancer, we will gain a lot of insight into that biological process,” Ji adds.

The research team will be delving at the molecular and cellular level to better understand the genomic features of the early precursors to stomach cancer. They want to know about the DNA and essential biological features that cause the cells to function one way or another.

If they can find the molecular features that are common to patients who will eventually develop gastric cancer, then they can use those features to say if a patient is at high risk for the disease. That patient can then be placed under surveillance with endoscopy more frequently than someone else whose risk is determined to be relatively low.

Stanford CARE supports the new study because of its significance for the study of gastric cancer among Asian populations. Pictured here: CARE leaders. 

Another research goal involves stem cells. Because the stomach is constantly under attack from acid and other harsh environmental items, its cells need to be replenished. It is known that the cancer precursors in the stomach have features of stem cells, which replenish the tissue by generating new cells.

“But these early cancer lesion precursors have stem cells that don’t look like what you'd normally find in a healthy stomach,” says Ji. “Because of that, we're using biological models to study those aberrant stem cells. We’ll be growing the cells in tissue culture so we can examine them at higher resolution with a group of tools that would not be feasible if we just simply looked at patient samples.”

International Aspects

While the focus of the project is mainly the United States, its results will also affect patients in Asia and South America as well. Resources from The Stanford Center for Asian Health Research and Education (Stanford CARE) are supporting the project because the center is focused on diseases that are prevalent in the Asian community, including stomach cancer.

In addition, the NCI established a study with other countries in South America because the prevalence of stomach cancer is so high there. As part of that NCI collaboration, the Stanford team is working with the University in Chile’s medical center to survey and collect samples from patients with the pre-malignant early stomach cancer precursor.

“That work has ramifications for our own U.S. population because patients have immigrated from places like South and Central America and Mexico,” Ji says.

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