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RET and Lung Cancer

Testing for an error in the RET gene helps your doctor understand your lung cancer and recommend treatments that may work better for you.

RET at a Glance:

  • Errors in the RET gene are one type of lung cancer biomarker.  
  • Biomarker testing can help match you to targeted treatments.
  • You can ask for testing at diagnosis or if treatment stops working.

Frequently Asked Questions about Biomarker Testing

What Is a RET Rearrangement?

An error in the RET gene is one type of lung cancer biomarker. There are two main types of errors in the RET gene:

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.

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 more 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. 

Dr. Justin Gainor discusses what patients need to know about the RET biomarker in lung cancer. This video was produced in 2021. For the latest treatment options, speak with your doctor.

Video transcript

Why RET Biomarker Testing Matters

Biomarker testing is essential for RET‑positive lung cancer because RET fusions are rare, require specific testing to detect, and directly determine whether a patient can receive highly effective RET‑targeted therapies. 

Biomarker testing looks for specific genetic changes in the tumor to help guide treatment. Testing includes DNA-based tests to identify changes in the genes themselves, and RNA-based tests to measure how those genes behave, giving your care team a fuller picture of your tumor makeup and available treatment options.

How Is RET Testing Done?

Testing is usually done at diagnosis or when treatment changes. Your doctor will need to test your tumor through a tissue or blood (liquid) biopsy. There are several different types of tests that doctors use to look for changes, or biomarkers in your cells:

  • Fluorescence in Situ Hybridization, or FISH, analysis is a common genetic test. FISH analysis looks at changes in the chromosomes through tissue under a microscope.
  • Immunohistochemistry (IHC) looks for proteins in the cell under a microscope.
  • Next-generation sequencing (NGS), also called comprehensive biomarker testing, is when tissue from a patient's tumor (gathered from a biopsy) is placed in a machine that looks for many possible biomarkers at one time.
  • Reverse transcription polymerase chain reaction (RT-PCR) is a laboratory method used to make many copies of a specific genetic sequence for analysis.

Your doctor may perform several of these tests at the same time to help confirm results. Different biomarkers rely more heavily on certain tests.

Testing for gene fusions is usually done using next‑generation sequencing (NGS) of DNA and RNA, which can identify many different fusion partners and confirm whether a fusion is present. 

Learn more about the different types of biomarker tests. 

Understanding Your RET Test Results

A RET‑positive result means your cancer has a RET fusion, a specific genetic change that can drive tumor growth and may make you eligible for highly effective RET‑targeted therapies. 

A RET‑negative result means no RET fusion was found, so treatments that specifically target RET‑driven cancers are unlikely to help. 

An unclear result means the test couldn’t confirm whether a RET fusion is present, and your care team may recommend repeat or more advanced testing, especially RNA‑based testing, to get a more accurate answer. 

How RET Results Influence Treatment

A RET rearrangement can help guide treatment decisions.

Knowing whether your lung cancer has 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 FDA-approved RET inhibitors include:

  • Selpercatinib (Retevmo)
  • Pralsetinib (Gavreto)

Learn more about targeted therapy treatment for lung cancer.

Over time, the cancer may change, and the RET inhibitor may stop working.

If this happens, your doctor might recommend:

Some patients may receive chemotherapy with or without immunotherapy first and a RET inhibitor second.

Researchers continue to study new treatments for RET-positive lung cancer. Ask your doctor whether a clinical trial may be appropriate for you.

Questions to Ask Your Doctor

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

  • What is the goal of this treatment?
  • What are the potential side effects?
  • 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.

What to Do After RET-Positive Lung Cancer Diagnosis

Someone with a RET-positive lung cancer diagnosis can take several empowering steps to stay ahead of their care. These are general medical information steps, not personal medical directives, and it’s important to work closely with a qualified healthcare professional for decisions about diagnosis or treatment. 

RET fusions are rare, so it helps to make sure your testing included broad next‑generation sequencing (NGS), especially RNA‑based testing, which is best at identifying the specific RET fusion partner. 

If you have a RET fusion, you may be eligible for highly effective targeted treatments, like selpercatinib or pralsetinib, as well as new therapies being studied in clinical trials; your care team can explain which options fit your situation. 

Keeping notes on how you feel helps your team support you, adjust treatment if needed, and make sure your care aligns with your goals and preferences. 

Support for Patients with RET-Positive Lung Cancer

Lung cancer research can move at a rapid pace. Always speak with your doctor about the most up-to-date treatment guidelines.

Medically reviewed by: Jorge Gomez, MD
Last reviewed: June 2026 

Page last updated: August 17, 2026

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