RET

RET-fusion positive lung cancer

About RET-fusion+ NSCLC

If you have been told that you have RET-fusion+ NSCLC, you might be wondering what this means.

Firstly, NSCLC stands for 'non-small cell lung cancer' – you can learn more about what this is here. About 85% of people with lung cancer have NSCLC.1

But what does RET-fusion+ mean? To understand that, we need to learn a bit more about 'DNA'.

Your body is made up of trillions of tiny building blocks called cells. Inside each cell is DNA. DNA is like a set of instructions that tell your cells what to do. They tell the cell to make certain things, when to grow or multiply, when to move around, and even when it is time to die.2

Normally your DNA helps keep your cells in a careful balance,3 so that they are multiplying and dying at a similar speed. But sometimes something goes wrong, and the DNA changes. This can cause cells to grow too fast and eventually make a tumour.2

RET-fusion+ means that you have a change in a small part of your DNA (the small part is called a ‘gene’) that makes a protein called RET (or 'rearranged during transcription'). This bit of DNA and the protein it makes are responsible for how certain parts of your body work, including your gut and your urinary system (kidneys and bladder).4

RET doesn’t exist in healthy lungs – the cells would normally ignore that bit of information in your DNA. But in RET-fusion+ NSCLC, the change in the gene means that your lungs cells start making a damaged version of the RET protein. When this happens, your cells start to grow and multiply out of control, and eventually they build up and become tumours.4

Only about 1% to 2% of people with NSCLC have a change in their RET gene.5 We don’t know exactly what causes the gene to change in somebody with RET-fusion+ NSCLC, but you can learn about some risk factors for lung cancer generally further down this page.


People who have RET+ NSCLC

People who are diagnosed with RET+ NSCLC tend to be:
  • Younger than a lot of other people diagnosed with cancer6–8
    People with RET+ NSCLC tend to be diagnosed when they are around 60. In comparison, most people with lung cancer are usually diagnosed around the age of 70
  • Never-smokers or light smokers6,7,9,10
    Many people who are diagnosed with RET+ NSCLC have only lightly smoked, or never even smoked at all

Risk factors for developing RET+ NSCLC

Right now, we don’t know exactly why some people develop a change in their RET gene.

While smoking and being exposed to second-hand smoke are some of the most well-known causes of lung cancer,11 people who develop RET+ NSCLC often have never smoked, or may have only lightly smoked, in the past.6,7,9,10

Developing lung cancer when you have little or no smoking history can be extremely frustrating, and you might find yourself looking for answers as to why you have developed lung cancer at all.

There are a number of other factors (summarised below) that are thought to be associated with the development of NSCLCs. However, it’s important to note that for some people, there may be no obvious cause as to why they have developed RET+ NSCLC.

Exposure to inhaled or ingested substances such as:
  • Asbestos12
  • Arsenic12
  • Non-tobacco smoke (e.g. burning buildings and wildfires, which may contain traces of metals and other carcinogenic substances)12
  • Diesel exhaust12
  • Metals such as chromium, beryllium, and nickel (you might be exposed to these if you work with car engines, or around smelting or welding, for example)12
  • Atmospheric pollutants13
Radiation exposure from:
  • X-rays, CT scans14
  • Radiotherapy to the chest area15
  • Radon exposure16
  • Exposure to radioactive fallout17
Family history/genetics
  • Although inheritance is not guaranteed, people with a family history of lung cancer are more likely to develop it than people without18
HIV infection
  • People with HIV are up to three times more likely to develop lung cancer than those without the infection19,20

How will my doctor know if I have a change in my RET gene?

Getting an accurate diagnosis is important, so your doctor will make sure that you have various tests to find out as much about your cancer as possible. That way, you and they can work together to create the best possible treatment plan for you.

Tests to see if you have a change in your RET gene will include a biopsy – you can learn more about these here.

You can learn more about how changes to your genes can cause cancer here.

Does having a change in my RET gene affect my prognosis?

Many people wonder what their prognosis is when thinking about what it means to have RET+ NSCLC. However, it can be hard for a doctor to give an exact amount of time, as cancer is a complex disease that can be affected by many different factors. These include:

  • Your age 
  • Your sex
  • Your race/ethnicity 
  • Where you live and work 
  • The type of work you do 
  • Your diet 
  • Your weight 
  • If you’ve ever smoked/how much alcohol you drink
  • Your family history of illnesses 

It’s worth being aware that RET+ NSCLC is considered more aggressive than some other forms of NSCLC21 – around half of all people who have advanced RET+ NSCLC (cancer that has spread, or ‘metastasised’, around the body) will get the cancer growing in their brain.9 With regular chemotherapy, about half of people with advanced NSCLC pass away within 2–3 years of their diagnosis.22

However, research has led to the discovery of modern treatments called ‘RET inhibitors’, which are specifically designed to treat RET+ NSCLC.5

These RET inhibitors are relatively new, but early clinical trials have shown that the tumours of most people who take a RET inhibitor start shrinking – including tumours in the brain.23,24

Click on one of the options below to learn more 


DNADeoxyribonucleic acid
NSCLCNon-small cell lung cancer
RETRearranged during transfection

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  2. Cancer Research UK. Genes, DNA and cancer. 2020. Available at: https://www.cancerresearchuk.org/about-cancer/what-is-cancer/genes-dna-and-cancer. Accessed October 2021.
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  4. Choudhury NJ & Drilon A. Transl Lung Cancer Res 2020; 9(6): 2571–2580.
  5. Stinchcombe TE. Ther Adv Med Oncol 2020; 12: 1758835920928634.
  6. Gautschi O et al. J Clin Oncol 2017; 35(13): 1403–1410.
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  8. SEER Cancer Stat Fact Sheets: Lung and Bronchus Cancer. Available at: https://seer.cancer.gov/statfacts/html/lungb.html. Last accessed October 2021.
  9. Drilon A et al. J Thorac Oncol 2018; 13(10): 1595–1601.
  10. Digumarthy SR et al. Cancers 2020; 12: 693.
  11. National Comprehensive Cancer Network (NCCN). NCCN clinical practice guideline in oncology: non-small cell lung cancer, Version v1 2022.
  12. Field RW & Withers BL. Clin Chest Med 2012; 33(4): 10.1016/j.ccm.2012.07.001.
  13. World Health Organization (WHO). Ambient (outdoor) air quality and health. 2018. Available at: http://www.who.int/en/news-room/fact-sheets/detail/ambient-(outdoor)-air-quality-and-health. Accessed October 2021.
  14. Berrington de González A et al. J Med Screen 2008; 15(3): 153–158.
  15. Friedman DL et al. J Natl Cancer Inst 2010; 102(14): 1083–1095.
  16. American Cancer Society. Radon and Cancer. 2015. Available at: https://www.cancer.org/cancer/cancer-causes/radiation-exposure/radon.html. Accessed October 2021.
  17. Shimizu Y et al. Radiat Res 1990; 121(2): 120–141.
  18. Schwartz AG & Ruckdeschel JC. Am J Respir Crit Care Med 2005; 173(1): 16–22.
  19. Shiels MS et al. J Acquir Immune Defic Syndr 2009; 52(5): 611–622.
  20. Winstone TA et al. Chest 2013; 143(2): 30–314.
  21. Shaw AT et al. J Clin Oncol 2009; 27(26): 4247–4253.
  22.  She T et al. Clin Lung Cancer 2020; 21(5): e349–e354.
  23. Drilon A et al. N Engl J Med 2020; 383(9): 813–824.
  24. Curigliano C et al. Abstract 9089 presented at the American Society of Clinical Oncology (ASCO) Annual Meeting; 4–8 June 2021; virtual format.