Genetic testing, which you may need to do, does not necessarily need to be done at the first visit. It is usually done in patients who have relapsed after surgery or are too advanced to have surgery, and it needs to be done before developing your next treatment strategy, especially planning to try targeted therapies, immunotherapy, to determine if you can benefit from it.
Cancer treatment has now become a five-pronged model of surgery, radiation, chemotherapy, targeted therapy, and immunotherapy. The first three have a relatively wide range of populations, but targeted therapy and immunotherapy are relatively precise and rigorous in the selection of the population of interest. This requires us to improve some special tests.
HER2 proto-oncogene testing to determine whether patients with adenocarcinoma can be targeted
Esophageal cancer is divided into squamous and adenocarcinoma, and 90% of our patients have squamous cancer, for which there is no better targeted therapy, except for an anti-epidermal growth factor receptor (EGFR) monoclonal antibody, nitrozumab. The only monoclonal antibody against EGFR, nitrozumab, is in clinical trials.
A relatively small proportion of patients with esophageal adenocarcinoma in China are eligible for targeted therapy, and the treatment regimen is primarily based on gastric adenocarcinoma.
Since it is called “targeted” therapy, we need to find the “target” before we can choose an effective drug, and this is where genetic testing is needed.
Studies have found that 10% to 30% of patients with gastric/esophageal cancer have amplified or overexpressed a proto-oncogene called HER2. For this group of patients, trastuzumab-targeted therapy combined with chemotherapy is significantly more effective than chemotherapy alone. For patients with advanced inoperable esophageal adenocarcinoma, testing for HER2 overexpression or amplification status is necessary for targeted therapy.
What is the HER2 proto-oncogene, or “human epidermal growth factor receptor 2”? When too much HER2 protein is present on the surface of cancer cells, it is called “HER2 positive” and stimulates cancer cell growth and proliferation.
Doctors usually obtain enough tumor tissue through surgery or gastroscopy to send it to a technically qualified laboratory for targeted testing through sequencing, fluorescence in situ hybridization (FISH), or immunohistochemistry (IHC). The following are targeted tests to detect abnormalities in specific genes.
Gene testing related to immunotherapy
Immunotherapy approaches for esophageal cancer are still in clinical trials. Immunotherapy is not effective for all patients, but is very effective for patients with certain characteristics. Screening of the advantageous population relies on a number of genetic tests, including:
- PD-L1 expression
- Microsatellite instability (MSI)
- Tumor mutational burden (TMB)
- Expression of mismatch repair proteins.
What do these medical terms mean?
1. PD-L1 is a protein expressed by cancer cells that inhibits the anti-cancer effects of immune cells when it binds to receptors on the surface of human immune cells. Studies have shown that immunotherapy (PD-1 / PD-L1 inhibitors) is more effective in patients with relatively high levels of tumor cell surface PD-L1.
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2. Microsatellite instability refers to the occurrence of mutations that cause some short and repetitive DNA sequences (microsatellites) to change in length due to defective self-repair mechanisms during DNA replication. It was found that a variety of solid tumors presenting with MSI had an overall efficiency of about 46% with PD-1 / PD-L1 inhibitors after failure of first-line therapy.
3. Tumor mutational load can be understood as how many mutations are carried on the DNA of tumor cells, and the higher its level, the better the efficacy of PD-1 / PD-L1 inhibitors usually is.
There are many markers being studied in addition to the three mentioned above. However, because the tumor microenvironment is so complex, more research is needed to accurately predict the efficacy of PD-1 / PD-L1 inhibitors.
Currently, immunotherapy research in esophageal cancer is focused on PD-1/PD-L1 inhibitors, but has not yet entered clinical use. in May 2017, pablizumab (Pembrolizumab) was approved in the United States for patients with metastatic or unresectable solid tumors with features of MSI-H or DNA mismatch repair defects. The drug is also available for patients with esophageal cancer with such features. Pabrolizumab is available in China, and you will need to consult your doctor if you can use it.