RET and Lung Cancer

What are RET gene rearrangements?

An error in the RET gene is one type of lung cancer biomarker. There are two main types of errors in the RET gene. One type is called RET point mutations. You can think of that as places where the DNA is misspelled. These mutations are often found in medullary thyroid cancer and not lung cancer. The other type is called RET rearrangements, or gene fusions. That is when a piece of DNA joins with another gene and creates a “fusion.” This fusion leads to uncontrolled cell growth and cancer. This is the most common RET gene error in lung cancer.

There are different types of RET rearrangements. The type depends on which gene is fused together with RET. The genes KIF5b, CCDC6 and NCOA4 are the most common fusion partners.

Who is most likely to have a RET rearrangement?

RET rearrangements appear in about 1-2% of patients with lung cancer and generally appear in adenocarcinoma non-small cell lung cancer. Patients who have RET rearrangements tend to be younger than the average patient with lung cancer and have little to no smoking history.

How do you know if you have a RET rearrangement?

There are several ways to detect RET rearrangements. One is called a FISH analysis which looks at changes in the chromosomes through tissue under a microscope. Another way is through next-generation sequencing (NGS). This type of comprehensive testing places tumor tissue that has been gathered from a biopsy into a machine that looks for many possible biomarkers at one time.

There may be some situations where a patient can’t undergo the biopsy needed to perform NGS, so a liquid biopsy is recommended instead. A liquid biopsy can look for certain biomarkers in a patient’s blood. Talk to your doctor to make sure one of these tests was performed.

Learn more about the different types of biomarker tests.

What is the course of treatment like for someone with a RET rearrangement?

Knowing if you have lung cancer with a RET rearrangement is important no matter your stage of lung cancer. However, it has the most treatment implications for advanced-stage lung cancer patients.

First-line treatment for RET rearrangements for advanced-stage lung cancer patients are specific drugs that target, or inhibit, RET. Currently, selpercatinib (Retevmo) and pralsetinib (Gavreto) are the two FDA-approved RET-inhibitors.

In time, the cancer is likely to evolve, and the RET-inhibitor may stop working. At that point, your doctor might recommend clinical trials, chemotherapy or immunotherapy. Some patients may receive chemotherapy with or without immunotherapy first and a RET-inhibitor second.

Work with your doctor to discuss your goals and options each time you have to make a treatment decision. The three big questions to ask are:

1. What is the goal of this treatment?
2. What are the potential side effects?
3. What other options do I have?

Research is happening at a rapid pace and your doctor should be up to date on the recommendations for your specific type of lung cancer. If you don’t feel comfortable with the answers you are receiving, do not hesitate to seek out a second opinion.