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Esophageal Cancer: What are Biomarkers and Immunotherapy?

How biomarker testing can help you and your healthcare team predict what cancer drugs will have the most benefit.

With esophageal cancer, biomarker testing is done by taking a biopsy, a tissue sample from the tumor, and testing the sample in a lab.

In the simplest terms, cancer is the uncontrolled growth and spread of cells. Under normal circumstances, the immune system regulates the life cycle of cells and destroys any cells that are behaving in an abnormal way—such as cells that are damaged, infected, or cancerous. But sometimes, cancer cells are able to grow in an uncontrolled manner because they are able to evade the normal mechanisms of the immune system.

Immunotherapy is an approach to treating cancer that helps the immune system recognize and destroy cancer cells. It is one of several cancer therapies that can be used in the treatment of esophageal cancer—cancer that begins in the cells of the esophagus, the hollow muscular tube that carries food and liquids from the throat to the stomach.

When is immunotherapy used?

Immunotherapy may be used when esophageal cancer cannot be treated with surgery—for example, when the cancer has spread outside the esophagus to other sites in the body, or if a person is at high risk for complications from surgery. Some immunotherapy drugs can be used in combination with other types of cancer treatments, such as chemotherapy and radiation therapy.

Is immunotherapy the same as targeted therapy?

Targeted therapy is another type of cancer treatment. Both immunotherapy and targeted therapy aim to minimize damage to healthy cells while only acting on cancer cells. However, these two types of therapy work in fundamentally different ways—immunotherapy helps the body’s immune system fight cancer, while targeted therapies attack cancer cells directly. Biomarker testing plays an important role in both immunotherapy and targeted therapy.

What is biomarker testing?

Biomarkers are genes, molecules, or other substances that are found in the body when a person has a specific disease—in this case, esophageal cancer. Testing for these molecules or substances can diagnose cancers and guide treatment decisions. With esophageal cancer, biomarker testing is done by taking a biopsy, a tissue sample from the tumor. This sample will be collected during an upper endoscopy, a procedure that uses a long, flexible device to examine the inside of the esophagus.

The sample will be tested in a lab. Tests will look for specific genetic mutations and/or measure the levels of specific proteins. These test results can help your healthcare team determine if immunotherapy or targeted therapy may be effective at treating the cancer—and if so, which type of drug should be used.

With esophageal cancer, there are three biomarkers a biopsy sample might be tested for—HER2, PD-L1, and MMR/MSI.

HER2

This is a protein that plays an important role in the normal growth of cells. Some cancer cells produce large amounts of this protein, which drives the growth and spread of more cancer cells. Testing may look at the levels of this protein or the number of copies of the gene that contain the instructions for making the protein. Esophageal cancer that tests positive for HER2 may be treated with targeted therapy drugs that target the HER2 protein.

PD-L1

This is an immune checkpoint protein. Immune checkpoint proteins prevent the immune system from attacking normal cells. Some cancers use this protein to disguise themselves as healthy cells and avoid attacks by the immune system. Immunotherapy drugs called checkpoint inhibitors disable this disguise, helping the immune system to attack the cancer.

MMR and MSI

Biomarker testing may also look for genetic changes called microsatellite instability (MSI) or mismatch repair (MMR). In some situations, cancers that test positive for these genetic changes may be treated with an immune checkpoint inhibitor.

Remember, treatment for esophageal cancer is different for every person. Your best source of information about a diagnosis and your treatment options will be your healthcare team.

Article sources open article sources

National Cancer Institute. What is Cancer?
NCI Dictionary of Cancer Terms. Programmed cell death.
Jing Liu, Minjing Hong, et al. Programmed Cell Death Tunes Tumor Immunity. Frontiers in Immunology. March 30, 2022.
Seong Keun Kim and Sun Wook Cho. The Evasion Mechanisms of Cancer Immunity and Drug Intervention in the Tumor Microenvironment. Frontiers in Pharmacology. May 24, 2022.
National Cancer Institute. Immunotherapy to Treat Cancer.
American Cancer Society. Immunotherapy for Esophageal Cancer.
American Cancer Society. Treating Esophageal Cancer by Stage.
American Cancer Society. Targeted Drug Therapy for Esophageal Cancer.
NCI Dictionary of Cancer Terms. Targeted therapy.
American Cancer Society. Tests for Esophageal Cancer.
National Cancer Institute. Biomarker Testing for Cancer Treatment.
NCI Dictionary of Cancer Terms. Biomarker testing.
NCI Dictionary of Cancer Terms. Upper endoscopy.
MedlinePlus. EGD - esophagogastroduodenoscopy.
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Purabi Dhakras, Nataliya Uboha, et al. Gastrointestinal cancers: current biomarkers in esophageal and gastric adenocarcinoma. Translational Gastroenterology and Hepatology, 2022. Vol. 5, No. 55.
NCI Dictionary of Cancer Terms. HER2.
NCI Dictionary of Cancer Terms. PD-L1.

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