Mapping Stomach Cancer Tumors for Better, More Precise Treatments

A team of Singapore scientists has made a significant discovery in understanding stomach cancer, a disease that remains one of the deadliest cancers worldwide. By using advanced mapping technologies, they created a detailed “atlas” of stomach tumors, revealing hidden patterns in how cancer cells behave, evolve and interact with their environment. These insights could lead to more precise, targeted treatments that improve survival rates and reduce side effects.

Their study findings, published in Cancer Discovery, bring scientists closer to developing new treatments that can be customized according to the specific characteristics of a patient’s tumor to more effectively target gastric cancer cells.

Using advanced experimental and computational methods, the team discovered distinct differences between cancer cells at the periphery and at the core of the tumor, providing valuable insights into how gastric cancer cells interact with their environment to grow and spread.

The research team from the Singapore Gastric Cancer Consortium, including doctors and scientists from Duke-NUS Medical School, the National University Cancer Institute, Singapore (NCIS) and the National University of Singapore Yong Loo Lin School of Medicine, also uncovered distinct evolutionary pathways of tumor cells, resulting in different immune responses driving tumor progression and treatment resistance.

Gastric cancer remains a formidable adversary, ranking as the fifth most common cancer and the third leading cause of cancer-related deaths worldwide, with more than one million new cases and close to 770,000 deaths each year. In Singapore, gastric cancer ranks among the top 10 causes of cancer-related deaths and claims about 300 lives[1] each year.

Combining state-of-the-art spatial technologies and genetic engineering tools

In this study, one of the most extensive of its kind, the team used recently available geospatial and genomic technologies to analyze 226 gastric cancer samples from 121 patients, from the National University Hospital and other institutes. Using a technology called spatial transcriptomics, they collated data from 2,000 microregions of the tumor samples, integrated with profiles of 150,000 single cells using single-cell RNA sequencing. Integrating these two approaches allowed the creation of a highly detailed map of gastric cancer tissues. The study spanned three years, from January 2022 to December 2024.

Professor Patrick Tan, a senior author of the study and Senior Vice-Dean for Research at Duke-NUS, said:

“The integration of spatial technologies and genetic engineering tools is like upgrading from an old roadmap to a high-tech GPS for cancer. Now, we can pinpoint exactly where cancer cells are in a tumor, how they behave and what makes them spread or stay put. This gives us a powerful tool to develop better treatments tailored to each patient, a tool with the potential to offer a valuable data resource for future exploration and discovery for scientists studying gastric cancer worldwide.”

Study findings: Identifying tumour subregions and evolutionary trajectories

The scientists identified two subgroups of cancer cells within the same tumor, with different surrounding types of immune cells and blood vessels that can contribute to tumor growth.

One subgroup comprised cells located at the tumor core. These cells were found to be marked by insufficient oxygen supply and were less likely to spread. The other subgroup, with cells located at the edge of the tumor, showed molecular features of highly invasive cells, which were more likely to spread.

By understanding such distinct interactions between tumor cells and their surrounding non-cancerous cells, researchers can identify critical pathways and genetic markers that influence tumor behavior. For instance, the team discovered that non-cancerous cells bordering cancer cells were in a unique state driven by transforming growth factor-beta (TGF-β) signaling, a critical pathway involved in cell growth, differentiation and immune response regulation. Targeting TGF-β signaling could inhibit the environment that promotes tumor growth and improve cancer therapy efficacy.

The team also uncovered separate evolutionary pathways that gastric cancers follow, each linked to specific prognostic outcomes. Taken collectively, these critical facets of tumor progression that the scientists identified, could expose gastric cancer’s Achilles’ heel, unveiling potential biomarkers for personalized therapies and offering differentiated treatment strategies to target various pathways.

Dr Raghav Sundar, one of the senior authors of the study and a senior consultant with the Department of Haematology-Oncology at NCIS, at the time of the research, explains:

“Our study breaks new ground in understanding the complex ecosystem of stomach cancer tissue with unprecedented spatial resolution. By employing advanced techniques, we've been able to meticulously map the interactions between various cell types within the tumor and its surrounding microenvironment of stomach cancer. This granular view allows us to see how cancer cells and their surrounding microenvironment influence each other and how this interaction drives tumor progression and resistance to treatments. These insights will be crucial in developing targeted therapies that can overcome the local barriers within the tumour microenvironment and effectively combat cancer.”

Armed with these new insights, the researchers are now working on identifying even more therapeutic targets for the treatment of gastric cancer and testing them in pre-clinical models. Their goal is to develop smarter, more effective treatments that can be tailored to each patient’s tumor type–moving closer to truly personalized cancer care.

Reference: Ma H, Srivastava S, Ho SWT, et al. Spatially resolved tumor ecosystems and cell states in gastric adenocarcinoma progression and evolution. Cancer Discovery. 2025:OF1-OF26. doi: 10.1158/2159-8290.CD-24-0605

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