04 Apr DUKE-NUS Study Detects Hidden Patterns in How Gastric Cancer Cells Behave

MedicalResearch.com Interview with:

Prof. Tan

Prof.  Patrick Tan MD PhD
A senior author of the study and
Senior Vice-Dean for Research at Duke-NUS

Dr. Sundar

Dr. Raghav Sundar MD PhD
A senior author of the study and a senior consultant with the Department of Haematology-Oncology at the National University Cancer Institute, Singapore
at the time of the research.

MedicalResearch.com: What is the background for this study? What are the gaps in knowledge that you were seeking to fill?

Response: Gastric cancer is a serious health issue worldwide and particularly prevalent in parts of Asia, Europe and South America. Gastric cancers are difficult to treat due to frequent resistance to therapies like immunotherapy. There are also many subtypes of gastric cancer, which can now be recognised based on their histological and molecular characteristics. However, recent studies have shown that besides differences between patients, there are also significant variations within a single tumour, further challenging successful treatment. Our study aimed to better understand these intricate interactions and variations occurring within gastric tumours, particularly how these differences evolve and impact the immune microenvironment and patient outcomes.

MedicalResearch.com: What are the main findings?

Response:  Our study discovered extensive diversity within tumours, revealing two main evolutionary paths in gastric cancer: branched evolution and internal diaspora evolution. Each path was associated with different molecular characteristics, immune microenvironments and clinical outcomes. By analysing tumour samples at a high resolution, the study highlighted specific genes and pathways active in these subgroups that could be targeted for therapy.

MedicalResearch.com: What is the significance of these findings? How will they ultimately benefit patients?

Response: Understanding the detailed landscape of tumour cells and their interactions with the immune system may help to develop better targeted therapies. Knowing the specific evolutionary paths and key genes involved can lead to personalised treatment plans, improving patient outcomes. For instance, identifying heightened activity in certain pathways may suggest new drugs or therapy combinations.

MedicalResearch.com: Are the gastric cancer tumor ecosystems influenced by bacteria in the stomach?

Response: This particular study focused more on the cellular and genetic interactions within the tumours and did not explicitly address the role of bacteria in the stomach. However, the interactions between different cell types and the immune environment within the tumour were key points of investigation, and it is possible that stomach bacteria may contribute to this process.

MedicalResearch.com: What was the main challenge you faced in your research and how did you overcome it?

Response: One major challenge was the complexity and diversity within tumours, which make it difficult to categorise and understand the intricate interactions at play. To address this, we used advanced technologies like spatial transcriptomics and single-cell RNA sequencing. These tools allowed us to examine the tumour ecosystems at a granular level, providing insights that would have been missed with conventional methods which tend to analyse tumours at a bulk aggregated level.

MedicalResearch.com: What should readers take away from your report?

Response: Readers should understand that gastric cancer is highly complex and varies significantly within each patient. By using advanced profiling techniques, the study revealed how different tumour regions evolve and interact with the immune system, leading to better-tailored treatments. The insights gained from this study can be crucial for developing precision medicine approaches in cancer treatment. 

MedicalResearch.com: What recommendations do you have for future research as a results of this study?

Response: Future research should continue to explore the detailed interactions within tumours using spatial and single-cell profiling techniques. Focus should be placed on understanding how different evolutionary paths and immune environments influence treatment resistance and patient outcomes. Additionally, further studies should investigate the specific roles of identified genes and pathways in tumour progression and therapy response.

MedicalResearch.com: What are the next steps for your research?

Response: The next steps involve further validating the findings in larger and more diverse patient cohorts. We aim to explore the potential of targeting specific pathways and genes identified in the study to develop new therapeutic strategies. There is also interest in expanding the analysis to other types of cancer to see if similar patterns and targets can be found.

Citation:

Haoran Ma, Supriya Srivastava, Shamaine Wei Ting Ho, Chang Xu, Benedict Shi Xiang Lian, Xuewen Ong, Su Ting Tay, Taotao Sheng, Huey Yew Jeffrey Lum, Siti Aishah Binte Abdul Ghani, Yunqiang Chu, Kie Kyon Huang, Yeek Teck Goh, Minghui Lee, Takeshi Hagihara, Clara Shi Ya Ng, Angie Lay Keng Tan, Yanrong Zhang, Zichen Ding, Feng Zhu, Michelle Shu Wen Ng, Craig Ryan Cecil Joseph, Hui Chen, Zhen Li, Joseph J. Zhao, Sun Young Rha, Ming Teh, Joe Yeong, Wei Peng Yong, Jimmy Bok-Yan So, Raghav Sundar, Patrick Tan; Spatially Resolved Tumor Ecosystems and Cell States in Gastric Adenocarcinoma Progression and Evolution. Cancer Discov 1 April 2025; 15 (4): 767–792. https://doi.org/10.1158/2159-8290.CD-24-0605

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Last Updated on April 4, 2025 by Marie Benz MD FAAD