The anaplastic lymphoma kinase (ALK) gene forms part of a person’s DNA. ALK genes can mutate anywhere in the body, but when this occurs in the cells of a person’s lungs, it can cause a type of lung cancer called ALK-positive non-small cell lung cancer.
In most cases, ALK-positive cancers affect the lungs. Non-small cell lung cancer is the most common form of lung cancer. Up to 1 in 25 people with non-small cell lung cancer have a diagnosis of ALK-positive lung cancer.
ALK-positive lung cancer usually affects people younger than 55 years who have never smoked. It affects females more frequently than males.
This article looks at ALK-positive non-small cell lung cancer in more detail, including the stages, testing, and treatment. It also considers the outlook for people with this form of cancer.
The medical community first discovered ALK-positive cancer in 2007. It happens when a person’s EML4 and ALK genes rearrange, creating a fusion oncogene called EML4-ALK. An oncogene is a mutated or abnormally expressed form of a gene that usually plays a role in cell growth. In this case, the changes to the ALK gene result in uncontrolled cell growth.
Most ALK-positive cancers happen in people with non-small cell lung cancer.
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People with non-small cell lung cancer should talk with a doctor about biomarker testing for ALK-positive cells. The results of the test will help the doctor determine the treatment options that are most likely to be effective.
In recent years, survival rates have vastly improved for people with ALK-positive cancers, including ALK-positive non-small cell lung cancer.
For example, 20 years ago, people with stage 4 ALK-positive non-small cell lung cancer had a 5-year survival rate of 2%. However, a 2018 study found that the median overall survival had reached 6.8 years among those who received the correct treatment. A median survival rate means that about 50% of participants in the study lived longer than this time.
The survival rate for people with ALK-positive non-small cell lung cancer continues to improve with advances in medical research.
However, the outlook for a person with ALK non-small cell lung cancer may vary depending on several factors. These include the type of treatment that a person receives and how their body responds to it. For instance, a
The typical symptoms of ALK-positive non-small cell lung cancer are the same as those of any lung cancer. They include:
- a persistent cough
- chest pain that gets worse if a person takes a deep breath, coughs, or laughs
- loss of appetite
- unexplained weight loss
- coughing up blood
- shortness of breath
Some people, including healthcare professionals, may not be aware that ALK-positive lung cancer mainly affects young people who do not smoke. Therefore, anyone with these symptoms should seek the advice of a doctor who knows about the condition. They will be able to order further testing if necessary.
The different stages of cancer refer to how much the cancer has grown and how far it has spread to other areas of the body.
People with ALK-positive cancer may not experience any symptoms until the cancer has reached stage 4. However, doctors may sometimes detect the condition at an earlier stage when carrying out a chest scan for another purpose.
The table below summarizes some simplified staging information from the American Cancer Society:
|Stage 0||The tumor is confined to the top layer of cells in the airways. It has not spread to deeper lung tissue, the lymph nodes, or any other body parts.|
|Stage 1A||The tumor has grown and can be 1–3 centimeters (cm) in diameter.|
|Stage 1B||The tumor is 3–4 cm in diameter and may be affecting deeper parts of the lungs.|
|Stage 2A||The tumor is 4–5 cm in diameter and may be affecting deeper parts of the lungs.|
|Stage 2B||The tumor is 4–5 cm in diameter, may be affecting deeper parts of the lungs, and has spread to the lymph nodes.|
|Stage 3A||The tumor is 5–7 cm in diameter and has spread further into the lungs.|
|Stage 3B||The tumor is beginning to affect the chest and the areas around the heart.|
|Stage 4||The cancer may have spread to the other lung and may have reached distant organs, such as the liver or brain.|
To test for ALK positivity, doctors must perform an examination on a person’s tissue or blood. Diagnostic testing methods may include:
- Biopsy: A doctor will remove a sample of a person’s lung tumor, which technicians will then test in the laboratory for signs of ALK positivity. Doctors may refer to this testing as next-generation sequencing or comprehensive biomarker testing.
- Liquid biopsy: This test involves examining the blood to look for DNA that could indicate the presence of tumors.
- FISH analysis: Examining cells from tissue or blood under a microscope allows doctors to detect any changes.
- Immunohistochemistry: This procedure involves looking for proteins in the tumor cells.
As ALK-positive non-small cell lung cancers may require slightly different treatment than other non-small cell lung cancers, testing for ALK positivity may be helpful for anyone with a lung cancer diagnosis.
Doctors treat ALK-positive non-small cell lung cancers in a variety of different ways.
One treatment that people may require soon after diagnosis is medication in the form of ALK inhibitors, such as:
- crizotinib (Xalkori)
- ceritinib (Zykadia)
- alectinib (Alecensa)
- brigatinib (Alunbrig)
- lorlatinib (Lorbrena)
However, once the cancer has progressed, taking an ALK-inhibitor may no longer be effective. A person can then discuss alternative options with their doctor, such as:
- Higher dosage: An initial option may be to try taking a higher dosage of the same ALK-inhibitor.
- Another ALK-inhibitor: Another biopsy may be necessary to check whether a person has developed an ALK resistance mutation.
- Chemotherapy: Doctors may recommend a type of chemotherapy called pemetrexed-based chemotherapy.
- Radiation therapy: Radiation therapy may be
especiallyuseful as a treatment for cancer that has not spread extensively.
- Clinical trials: A person may wish to try newer treatments during clinical trials.
ALK-positive non-small cell lung cancer usually occurs in young people who have never smoked.
An early diagnosis allows doctors to prescribe the most effective treatment before the cancer progresses extensively. Advances in medical research mean that the outlook for people with ALK-positive non-small cell lung cancer is steadily improving.