- Session: Precision medicine in GI cancer. ESMO GI Congress 2024, 28.06., 11:15 h/ Rodrigo Dienstmann (Barcelona, Spain).
Various biomarker tools play a crucial role in the treatment of gastrointestinal (GI) malignancies. Genomic tests, especially multigene assays, are important for the diagnosis of biliary, pancreatic and colorectal cancers. Immunohistochemistry, such as the analysis of HER2 amplification and PD-L1 expression, also contributes to the identification of potential therapeutic approaches. Mismatch repair deficiency (dMMR), microsatellite instability (MSI) and Epstein-Barr virus (EBV) positivity extend the range of diagnostic tools available.
There are numerous known biomarkers for colorectal carcinomas that are used for the development and application of targeted therapies. An important biomarker for the application of immunotherapies is MSI/dMMR. Compared to other GI malignancies, gastric and hepatocellular carcinomas have fewer known genetic biomarkers. Only tumours with a high tumour mutation burden (TMB) are more treatable. An emerging biomarker for immunotherapies in gastric cancer is EBV positivity. Other new biomarkers that show promise for the development of future therapies include FGFR2b and CLDN18.2.
New technologies enable detailed analysis of protein expression in tumour tissue. Antibody-drug conjugates combine targeted antibodies with cytotoxic agents, leading to more effective treatment. Quantitative and multiplex assays allow the simultaneous measurement of multiple biomarkers, enabling a more comprehensive analysis. Immunotherapy-related biomarkers such as digital pathology and spatial cell phenotyping are also promising approaches.
Digital pathology, combined with artificial intelligence, opens up new possibilities for analysing and interpreting tissue samples. One example of the virtual representation of gene expression signatures is the atezolizumab bevacizumab response signature (ABRS). This technology can provide precise insights into tumour biology. These signatures are then transferred to histological sections and validated in independent cohorts. Other examples include quantitative assays to determine ERBB2 expression and the field of metagenomics, which could offer new possibilities for modulating the gut microbiome.
Digital pathology, coupled with artificial intelligence, could enable quantifiable and reproducible tissue biomarkers to be integrated into clinical practice. The phenotyping and spatial distribution of tumour cells and their microenvironment using multiplex assays will drive the development of immunotherapeutic approaches. Finally, quantitative assays for the determination of cancer cell targets offer promising tools for the development of antibodies and antibody-drug conjugates.