A rearranged during transfection (RET) inhibitor is a relatively new targeted therapy that can help people with certain types of lung cancer.

Share on Pinterest
xavierarnau/Getty Images

This treatment attacks a specific protein involved in the RET gene. Gene mutations can cause a cancerous tumor’s DNA to change and grow in 1–2% of people with lung cancer.

RET inhibitors target cancers that have RET gene mutations. These include non-small cell lung cancer (NSCLC), medullary thyroid cancer, and papillary thyroid cancer.

In recent years, clinical trials and research studies have produced promising results regarding the use of RET inhibitors for people with lung cancer.

This article will look at how RET inhibitors work, how they may help people with lung cancer, their potential side effects, and more.

RET inhibitors are a relatively new treatment option for NSCLC, which is the most common form of lung cancer, and two types of thyroid cancer.

The RET gene gives instructions to produce a protein involved in cell signaling. This protein is necessary for the regular development of nerve cells.

RET point mutations are more common in thyroid cancer. In NSCLC, the RET gene can have an error, leading to a mutation known as a RET arrangement or gene fusion.

This can cause uncontrolled cell growth and cancer. People who experience this are typically younger and have little to no smoking history.

There are two ways for a doctor to determine whether or not a person requires treatment with a RET inhibitor. One is a comprehensive next-generation sequencing test. This tests tissue taken from a person’s tumor during a biopsy. The second way is a liquid biopsy. This looks for changes in DNA that cause cancer cells to grow.

Research is ongoing to determine the full benefits of these treatments and their long-term effectiveness.

There are currently two RET inhibitors available to treat lung cancer.

The Food and Drug Administration (FDA) approved the first one, selpercatinib (Retevmo), in May 2020. This is for people with NSCLC or either of the two types of thyroid cancer mentioned above. It is an oral medication that a person takes twice per day.

The FDA approved a second drug, pralsetinib (Gavreto), later that year. People take this treatment orally once per day.

A person can receive either of these treatments regardless of the previous types of cancer treatment they have undergone.

Researchers have seen early success with selpercatinib and pralsetinib. More than half of people who had undergone previous cancer treatment experienced some amount of tumor shrinkage with selpercatinib. Initial treatment with this therapy led to an overall response rate of more than 80%.

For pralsetinib, 57% of people who had previously received treatment experienced tumor shrinkage, and 70% of people who had never received treatment experienced a reduction in tumor size.

Additional research is necessary to determine why some people with NSCLC respond to these treatments and others do not.

Treatment resistance is another issue that researchers are investigating. In one study, researchers found that some people who had developed a resistance also experienced mutations in MET or KRAS genes.

Therefore, scientists may need to focus on newer treatments or combination treatments to address these mutations.

Researchers have also tried other targeted therapies — including cabozantinib, lenvatinib, sunitinib, nintedanib, and vandetanib — to treat cancer with RET alterations. However, trials have found only limited benefit for people with this type of NSCLC.

RET inhibitors can eliminate cancerous growths or lead to partial tumor shrinkage. However, some people who use RET inhibitors to treat NSCLC may experience side effects.

Some potential side effects include:

  • dry mouth
  • diarrhea or constipation
  • fatigue
  • high cholesterol
  • high blood pressure
  • feeling tired
  • swelling in the hands or feet
  • rash
  • high blood sugar levels
  • muscle and joint pain
  • low white blood cell, red blood cell, or blood platelet counts
  • changes in the results of certain other blood tests

If a person notices any of these side effects, they should contact a doctor immediately.

While RET inhibitors are still undergoing research, early results have been promising.

Though RET mutations affect a relatively low percentage of people with NSCLC, research has shown that the two currently approved RET inhibitors have the potential to help people with this type of cancer.