RET and Lung Cancer

When tumor tissue is looked at under a microscope, physicians can see what type of cancer it is. But physicians can also look for changes in the DNA of the tumor that might be causing the tumor to grow. Sometimes these changes are called biomarkers or molecular markers.

One way to think about it is that our DNA is like an instruction manual. If there is a typo in the instruction manual, the cell receives wrong instructions and can grow into cancer. Biomarker testing looks for those typos, so physicians know if you are a candidate to receive a targeted therapy that directly addresses those typos. 

An error in the RET gene is one biomarker that physicians look for in non-small cell lung cancer. If you have non-small cell lung cancer, it is important to talk to your doctor about comprehensive biomarker testing to see if you have an error in the RET gene or another biomarker. The results of this testing influence your treatment options. To learn more about biomarker testing, visit Lung.org/biomarker-testing. 

What are RET gene rearrangements?

There are two main types of RET genetic alterations, or errors in the gene.  One is called RET point mutations.  You can think of that as places where the DNA is misspelled. Those are often found in medullary thyroid cancer. The other is called a RET rearrangement or gene fusion. 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 (or joined) with RET. The gene KIF5b is the most common fusion partner, and CCDC6 is second most common.

Who is most likely to have a RET rearrangement?

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

How do you know if you have a RET rearrangement?

In general, there are two ways to detect RET rearrangements. The best way is through comprehensive next-generation sequencing (NGS). This type of testing places tissue from a patient’s tumor (gathered from a biopsy) in a machine that looks for a large number of possible biomarkers at one time. There may be some situations where a patient can’t undergo the biopsy needed to perform NGS, and so liquid biopsy is recommended. 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 here.

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 but has the most treatment implications for stage four patients. 

First-line treatment for RET rearrangements for stage four patients are specific drugs that targets or inhibit RET. Currently selpercatinib and pralsetinib are the two approved RET-inhibitors.  Within a few months to years, the cancer is likely to evolve, and the RET-inhibitor may stop working. At that point, your doctor might recommend clinical trials of other RET inhibitors or chemotherapy with or without immunotherapy. 

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.