Stomach Cancer Biomarkers

A biomarker, or biological marker, refers to any biological characteristic that can be measured and evaluated objectively. They can be found in your tissues, blood or other bodily fluids (e.g., saliva and urine). Examples of biomarkers used in clinical practice include your blood pressure and heart rate.

Biomarkers serve as indicators of normal or abnormal processes, conditions or diseases, such as cancer. In oncology, biomarkers can come in the form of proteins, genetic material like DNA and RNA, and many other biological molecules derived from your bodily fluids and tumor tissues.

These biomarkers are typically involved in the formation of cancer or are released due to the presence of the disease. Therefore, testing for cancer biomarkers in your blood or tissue samples can reveal important details about the cancer you’ve been diagnosed with. This knowledge helps your doctors understand the processes involved in the progression of your disease.

Biomarkers can be classified in many ways, be it according to their characteristics or applications. In this article, the biomarkers commonly associated with stomach (or gastric) cancer are grouped into two categories: established and emerging.

Established gastric cancer biomarkers

The three molecular biomarkers that are well-established in gastric cancer are human epidermal growth factor receptor 2 (HER2), programmed death ligand 1 (PD-L1) and microsatellite instability (MSI).

HER2 is a protein encoded by the ERBB2 gene. Originally, it was associated with poor outcomes for gastric cancer. However, HER2-targeted therapy has also showcased better responses to cancer treatments and longer survival. Now, HER2 is a major predictive biomarker for managing gastric cancer.

> Learn more about HER2 as a gastric cancer biomarker

PD-L1 is a protein found on the surface of certain healthy cells in your body. In normal circumstances, it functions as a ‘brake’ to prevent your immune system from attacking normal and healthy cells. However, certain cancer cells, like those of some gastric tumors, produce excessive amounts of PD-L1 to avoid detection and attack from your body’s immune response.

Immunotherapeutics like nivolumab and pembrolizumab work by blocking PD-L1 proteins on the surface of certain gastric cancer cells, preventing them from breaking the immune system. This enables the immune system to recognize the cancer cells and activate immune cells to kill them. For this reason, people who have gastric tumors that overexpress PD-L1 respond better to immunotherapy than those with gastric tumors that have normal levels of PD-L1.

> Learn more about the gastric cancer biomarker PD-L1

Microsatellite instability (MSI) refers to the accumulation of DNA mismatches in short, repeating DNA sequences called microsatellites. MSI typically occurs due to the dysfunction of mismatch repair (MMR) protein, about 1/6 of which are caused by mutations in your MMR genes; as a result of this, any DNA mismatches occurring in microsatellites can no longer be rectified. For this reason, MSI is also called mismatch repair deficiency. High MSI (MSI-H) or MMR deficiency can lead to the inactivation of genes responsible for regulating cell growth and division. As a result, affected cells can start to divide uncontrollably and turn cancerous.

MSI is a biomarker associated with many cancers including colorectal and gastric cancer. It is well-known as a predictive biomarker because MSI-H gastric tumors are more likely to respond to immunotherapy. This is because tumors with MSI-H are more likely to be recognized by immune cells as a result of poor mismatch repair and the accumulation of numerous genetic abnormalities. MSI is also a prognostic biomarker as MSI-H tumors possess a better prognosis than MSI-low or MSI-negative tumors.

> Learn more about MSI as a gastric cancer biomarker

Emerging and potential gastric cancer biomarkers

With the success of biomarker-driven targeted therapies, mounting research has gone into discovering novel biomarkers that are elevated in gastric cancers and can be targeted for personalized treatment. Emerging and potential molecular biomarker in gastric cancer are Claudin18.2 and fibroblast growth factor receptor 2b (FGFR2b), respectively.

Claudin18.2 is a protein aberrantly expressed on the surface of cancerous gastric epithelial cells. It disrupts the tight junctions between the cells, affecting numerous cell signaling pathways, some of which are involved in cancer progression. In this manner, Claudin18.2 may contribute to various tumorigenic processes, such as tumor cell proliferation and migration. Identified as an emerging predictive gastric cancer biomarker, Claudin18.2’s abnormal overexpression in gastric cancer makes it an attractive and novel target for cancer therapy. Research has led to the emergence of zolbetuximab, a monoclonal antibody drug that targets Claudin18.2.

> Find out more about Claudin18.2 as an emerging gastric cancer biomarker

FGFR2b is a protein predominantly expressed in your body’s epithelial cells. Its activation sets off a cascade of signals between multiple proteins within the epithelial cell, culminating in the promotion of cellular processes that stimulate cancer progression. This prognostic and predictive gastric cancer biomarker is being studied as a potential therapeutic target. Clinical trials are currently testing a promising new drug called bemarituzumab, which targets the biomarker FGFR2b.

> Read more about the emerging gastric cancer biomarker FGFR2b