New Strategies for Molecular Classification in Gastric Cancer

At the 2023 World Congress on Gastrointestinal Cancers, Patrick Tan, MD, PhD, Genome Institute of Singapore, Singapore, gave a keynote lecture on new strategies to achieve molecular classification in gastric cancer that can potentially inform the future treatment landscape.

Looking to the future Dr Tan stated “the next challenge of gastric cancer classification will involve categorizing and classifying the tumor in microenvironment in a way that we can now begin to understand gastric cancers as a collective tumor ecosystem.”

Transcript:

Hello, my name is Patrick Tan and I'm from Singapore, and it was my great honor to give a keynote address at this year's World GI Congress. We are a basic science lab, but in my talk, what I focused on were new strategies to achieve a molecular classification of gastric cancer that may inform how we treat gastric cancer patients in the future.

My talk focused on three main areas. In the first area, I updated the audience on what is the current standard of molecular classification, drawing reference to large scale consortia like the Cancer Genome Atlas, TCGA. I made the point that many of these classifications currently used are largely based on changes to the DNA genomic alterations, and the challenge now was how to link these classifications to therapies that may improve the outcomes for different categories of gastric cancer patients. We have opportunities for some of these categories, like MSI-high gastric cancer with regards to immunotherapy, but there are other subtypes, like the genome stable subtype, for which we still urgently need new therapeutic options.

In the second part of my talk, I then challenge the audience to think beyond the genome, to look about other classifications that may reveal tumor biology at the level of gene expression or the epigenome. I highlight certain new findings from our group whereby studying the epigenome of gastric cancers, we were able to show that there is a specific new poor-prognosis subtype of gastric cancer called EMT-positive or, mesenchymal GC, that is driven not by genomic alterations, but by alterations in the epigenome, catalyzed by a master regulatory transcription factor called T1. Importantly, T1 appears to be a driver, not just in mesenchymal type gastric cancer, but in many categories of metastatic gastric cancer, such as those associated with peritoneal metastasis.

In the final part of my talk, I actually peered into the crystal ball and tried to illustrate how new emerging technologies like single cell analysis and spatial technologies might present new weapons that oncologists can use to refine and treat gastric cancer patients. I described a first-generation atlas of gastric cancer single cell profiles that we published where we looked at how to use this information to analyze intrapatient heterogeneity or heterogeneity that occurs within a single gastric cancer. We understood how using single cell profiles allows us to elucidate potential cell of origins of gastric cancer and also how by looking at single cell profiles of the tumor microenvironment, we are beginning to see that there are different categories of stroma, of fibroblasts, of immune cells that collectively we must all understand in order to inform the treatment of individual patients. Thus, we feel that while the current molecular classifications of gastric cancer are a good start, the next challenge of gastric cancer classification will involve categorizing and classifying the tumor in microenvironment in a way that we can now begin to understand gastric cancers as a collective tumor ecosystem.

I'd like to thank all the organizers of ESMO for allowing me to present this work and also all of the audience, and hope you have a wonderful conference. Thank you very much.

Source:

Tan P. Keynote Lecture: Molecular Classification of Gastric Cancer. Presented at the 2023 World Congress on Gastrointestinal Cancers; June 28-July 1, 2023; Barcelona, Spain.