A team of Singapore scientists has made a breakthrough in understanding stomach cancer, one of the deadliest cancers globally. Using advanced mapping technologies, they created a detailed “atlas” of stomach tumours, revealing hidden patterns in how cancer cells behave and interact with their surroundings. These findings, published in Cancer Discovery, offer hope for the development of personalised, more effective treatments that could improve survival rates and reduce side effects.

The research, led by the Singapore Gastric Cancer Consortium (SGCC), included experts from Duke-NUS Medical School, the National University Cancer Institute Singapore (NCIS), and the National University of Singapore Yong Loo Lin School of Medicine. By analysing 226 gastric cancer samples from 121 patients between January 2022 and December 2024, they used spatial transcriptomics and single-cell RNA sequencing to create a highly detailed map of gastric cancer tissues.

Professor Patrick Tan, Senior Vice-Dean for Research at Duke-NUS and a senior author of the study, likened this advancement to upgrading from an old roadmap to a high-tech GPS. He 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 are able to precisely locate the location of cancer cells within a tumour, understand their behaviour, and identify factors that contribute to their spread or stability. This discovery gives us a powerful tool to develop better treatments tailored to each patient.”

The study revealed two distinct subgroups of cancer cells within the same tumour—those located at the core and those at the periphery. Cells at the core, deprived of oxygen, were less invasive, while those at the periphery showed molecular features of highly invasive cells, making them more likely to spread.

Further analysis indicated that non-cancerous cells surrounding these cancerous cells exhibited unique molecular states driven by transforming growth factor-beta (TGF-β) signalling. TGF-β plays a critical role in cell growth, differentiation, and immune response regulation. Targeting this pathway could potentially inhibit the environment that supports tumour growth, making cancer therapies more effective.

The team also uncovered separate evolutionary trajectories followed by gastric cancers, each associated with specific prognostic outcomes. By identifying these pathways, researchers can develop biomarkers that guide personalised therapies and help target various pathways more effectively.

Dr. Raghav Sundar, a senior consultant at NCIS and author of the study, emphasised the importance of understanding these interactions. He stated:

“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 tumour and its surrounding microenvironment. These insights will be crucial in developing targeted therapies that can overcome the local barriers within the tumour microenvironment and effectively combat cancer.”

Gastric cancer is the fifth most common cancer and the third leading cause of cancer-related deaths worldwide, with over one million new cases and nearly 770,000 deaths annually. In Singapore, it remains among the top 10 causes of cancer-related deaths, claiming around 300 lives each year.

This study marks a paradigm shift in stomach cancer research. By offering unprecedented insights into tumour biology and its interaction with the microenvironment, the findings lay a strong foundation for developing precision medicine approaches. Tailored therapies that target distinct cancer subgroups and their evolutionary pathways could revolutionise gastric cancer treatment, potentially improving survival outcomes for thousands of patients. However, translating these discoveries into clinical applications will require sustained collaboration between researchers, clinicians, and policymakers.