Rarer than other forms, ALK+ lung cancer often affects young patients who have never smoked. It is hard to detect, but targeted therapies have transformed the outlook for patients.
By Ludivine Ponciau · Le Vif, print edition of 20 August 2026 · translated from French
It started with a cough that didn’t seem like much, as spring arrived. Véronique thought it was a seasonal allergy, even though at 53 she had never had one. The symptoms persisted, and even got worse, as the weeks went by. In May she went to her GP, who diagnosed atypical pneumonia — a lung infection caused mainly by bacteria — and prescribed antibiotics. One box, then a second… the cough would not go away. “It can take time,” the doctor insisted.
Véronique had a hunch that they needed to look further. In July she went to the emergency department. A first X-ray confirmed the initial diagnosis. She insisted on having a CT scan. A second diagnosis followed: tuberculosis. Then a third: sarcoidosis (a chronic inflammation that is not cancer). Transferred to another hospital, she had a bronchoscopy. “The next morning, the doctor came into my room to tell me I had lung adenocarcinoma [editor’s note: the most common form of lung cancer]. I thought: OK, that’s it for me. I could already see myself dying, and I was wondering how I was going to tell my children.” The doctor tried to reassure her: chemotherapy and immunotherapy can give very good results.
Following her instinct once again, she turned to another hospital. The oncologist who saw her ordered further tests. “Ten days later the verdict came in: I had the famous ALK fusion. That changed everything about how I approached this cancer, because the treatment was completely different. I could start straight away on a targeted therapy that comes down to taking one tablet a day, with side effects that are much less severe than with chemotherapy or immunotherapy.” What also gives her hope is that ALK-fusion lung cancer (ALK+) responds better to treatment than other forms of lung adenocarcinoma.
Rare and hard to detect
Discovered a little under twenty years ago, this very rare form of lung cancer is still not well known, including among medical professionals, and it is particularly hard to detect, especially at an early stage.
In around 85% of lung cancer cases, the diagnosis is non-small cell lung cancer (NSCLC). The remaining 15% are small cell lung cancers (SCLC). NSCLC is mainly linked to smoking, but other risk factors can also play a part, such as air pollution or exposure to certain substances, including radon. Adenocarcinoma is the most common subtype of NSCLC, accounting for 55% to 60% of cases. Among adenocarcinomas, tumours with a rearrangement of the ALK gene (ALK+ lung cancer) form a rare subgroup, representing around 3% to 5% of all NSCLC.
ALK+ lung cancer has several distinctive features: it often occurs in patients who are younger than average and who have smoked little or not at all, and it has a strong tendency (in 40% of patients) to develop brain metastases over the course of the disease. It also affects more women than men.
“The most common symptoms are paresis — reduced strength in an arm or a leg — bleeding in the brain or epileptic seizures. As with all other lung tumours, weight loss, a cough that brings up blood-stained mucus and difficulty breathing are also among the first signs,” explains Dr Mariana Brandão, an oncologist specialising in thoracic cancer at the Jules Bordet Institute. Despite these clues, ALK+ lung cancer remains hard to identify. Some patients, like Véronique, go through a long and anxious search for the right diagnosis before they can put a name to their illness.
To find out whether a lung tumour is ALK-positive (ALK+), doctors need to analyse cells from the tumour by taking a biopsy. The difficulty is that the sample is sometimes too small (too little genetic material), hard to obtain because the tumour is difficult to reach, or taken from a part of the tumour that is necrotic. The biopsy makes it possible both to confirm that it is lung cancer and to identify the type (adenocarcinoma or squamous cell carcinoma), by looking for certain characteristic proteins in the cells. The PD-L1 protein, a key biomarker in lung cancer, gives an indication of how likely a patient is to benefit from immunotherapy. The tumour is also tested for certain genetic abnormalities, including the ALK abnormality. This requires extracting DNA and/or RNA from the tumour cells.
If the tumour is indeed ALK+, treatment can be a targeted therapy rather than conventional chemotherapy or immunotherapy. Knowing quickly which type of cancer it is can therefore completely change the choice of treatment.
ALK can be tested for directly using a rapid technique called immunohistochemistry (IHC), which identifies the ALK protein in the tumour cells. If the result is very strongly positive, that can be convincing enough to start a targeted therapy against ALK. However, because false negatives are possible, these results have to be confirmed by genetic analysis.
“Third-generation targeted therapy is the treatment that gives the best results, particularly in patients who have not previously received first- or second-generation inhibitors and whose tumour is more resistant to treatment. The results are particularly encouraging, with seven-year progression-free survival of more than 50%, which is quite remarkable,” the oncologist explains.
While it can be treated relatively well, the exact causes of ALK+ lung cancer are still unexplained. Studies are under way to try to find out what might trigger it. One of them, in which the Bordet Institute oncologist is taking part, is being run by the EORTC, the European Organisation for Research and Treatment of Cancer. Called “Bio Radon”, it is studying the effects on the human body of exposure to radon, a radioactive gas found naturally in the ground, particularly in the south of Belgium. “We give our patients detectors so that they can measure the level of radon in their homes. At this stage it is only a hypothesis, but this gas could indeed be a risk factor for developing cancers with genetic abnormalities such as ALK+.”
Lifestyle
A cancer diagnosis always comes as a violent shock to the patient — even more so for someone who has always taken care to live healthily, hoping to protect themselves from serious illness.
The patients Dr Brandão sees in her clinic often express anger at a cancer that seemed to come out of nowhere. “The idea that only people who smoke can get lung cancer is still very widespread, and it is clearly wrong. Unfortunately it can affect anyone, even people who don’t smoke, who live healthily and who exercise. The same is true of blood cancer or pancreatic cancer.”
Véronique, who had always made sure never to light a cigarette, never drank too much and always avoided fast food and ultra-processed foods, felt that sense of injustice too. But she found the strength to move past it and to “work on her mindset”, turning this ordeal into a lesson. “I tell myself that if this happened to me, it’s because it was time for me to change some things in my life.” She did, however, have to face clumsy and even hurtful reactions from people around her when she told them about her illness, along the lines of “Oh, I actually know someone who died of that last year” or “What’s your prognosis?”. Because targeted therapy causes fewer side effects, her apparent good health hid the inner battle she was fighting, and signs of support became rarer.
These disappointments did not stop her from bouncing back. She read up on her illness, on the treatments and on what she could do to feel better. Along the way she found a support group for patients with the same atypical form of lung cancer: ALK Positive Belgium. “I took up new habits focused on well-being, to give myself every chance of recovering. I get out into the daylight, I go for walks in the woods, I’ve favoured certain foods. All these changes have helped me enormously with my mental health, which suffers a great deal.”
“It may sound like a bit of a cliché,” Dr Brandão agrees, “but a healthy lifestyle improves the health of the digestive system and the immune system, and therefore patients’ quality of life. These benefits are documented in studies. However, patients are often tempted to turn to food supplements that cost a fortune rather than change their habits. As a doctor, it is important to have an open conversation with them about this, so that we can help them as well as we can on this very difficult journey.”
Véronique feels lucky to have been able to rely on her instinct — when she insisted that the doctors look for the cause of her cough — and on her ability to bounce back after the diagnosis, so that the situation would be “easier to live with for everyone”. Today, when she sees her reflection in the mirror, she sees someone “who is doing well”. The hardest thing to deal with is the uncertainty after the scan she has every three or four months. And the fear of “only just missing” the miracle drug that will cure patients rather than keep them alive. “Everything is uncertain, but you have to believe. Either I fight, or I die.”