Genetics improves understanding of lung cancer

Genetics improves understanding of lung cancer

Genetics improves understanding of lung cancer

Lung cancer is predominantly detected in an advanced tumor stage. A cure is then unlikely. Yet, thanks to scientific advances, much has been done for patients with advanced lung cancer in recent years. Genetics in particular has helped to better understand the disease and to develop new treatment options.

These new treatment options are often referred to as “personalized” or “individualized” therapies. But what is behind it? Of course doctors have always treated individually. There is a difference between a younger or an older patient, a patient with or without complaints, and whether there are other diseases. The tissue type of the lung tumor ( non-small cell / small cell ) and the stage of the disease also provide important information on which therapy is best suited.

What genetic information is hidden in the tumor?

However, it is also possible to investigate the tumor genetically. This means, in the pathological laboratory, it is examined whether certain genes have defects (so-called mutations) which can lead to the development of lung cancer. These changes are also referred to as biomarkers. Usually, there are suitable drugs that counteract the genetic defect. They block the mutated parts of the tumor cell and thus prevent further spread of the tumor. Since, unlike in chemotherapy, the tumor is directly addressed, these drugs are also referred to as targeted therapies. By “personalized” or “individualized” is usually meant that the choice of treatment depends on the specific mutation of the tumor. As a result, the same disease may require different therapies.


For patients with non-small-cell lung cancer (NSCLC) and an EGFR mutation or ALK fusion, drugs are already approved:

What is an EGFR mutation?

In some patients a mutation of the EGF receptor (epidermal growth factor receptor) is found. The EGF receptor is located in the cell membrane and has a “docking site” on the outer side. When a particular protein is applied to the mutant receptor, growth signals are amplified. A mutation of the EGF receptor thus leads to the fact that tumor cells can grow uncontrollably and multiply. In approximately ten percent of all lung cancer patients, this genetic deviation can be demonstrated, which are then “EGFR mutation positive”. Interestingly, these patients have a slightly better prognosis (prognosis) per se than patients in whom this mutation is not found. EGFR mutations are particularly common in women, non-smokers, in patients with adenocarcinoma, and in stage IV.

What therapies can help?

Currently, there are three active ingredients (gefitinib, erlotinib, afatinib) in tablet form which the doctor can prescribe. They block the EGF receptor and prevent further growth signals from being emitted. These active ingredients are summarized under the heading EGFR tyrosine kinase inhibitor (EGFR-TKI). In all, studies have shown that they delay the growth of the tumor and thus the progress of the disease for a certain time. In studies, this figure was almost one year. Since this is a so-called median value, which has been calculated from the data of many patients, it is quite possible that a lung cancer patient also benefits from the therapy longer. In comparison, tumor growth in patients with chemotherapy could only be postponed by six months. In addition, it could be shown that patients have a better quality of life than chemotherapy. In the case of an active substance, it has now been shown that the patients also live longer when compared to chemotherapy. Most common side effects of EGFR tyrosine kinase inhibitors are skin rashes and diarrhea. In patients without EGFR mutation, the drugs have no effect.

What does an ALK fusion mean?

Patients with advanced NSCLC may also have fusions of the so-called ALK gene. The gene provides the blueprint for a particular enzyme, the anaplastic lymphoma kinase (ALK), and can induce proliferation of cells when activated by fusion with another gene. The resulting cancer gene is referred to as ALK fusion.

What therapy can help?

There is also a corresponding therapy (Crizotinib), a so-called ALK inhibitor, which is available in capsule form. About 3 to 5% of lung cancer patients are ALK-positive. With the ALK inhibitor, the tumor growth in the admission study could be stopped by just under eight months. In addition, the quality of life of patients improved. Common side effects are blurred vision, gastrointestinal symptoms such as vomiting, nausea or constipation as well as an increase in liver values. Also here: The drug can only help patients in whom the ALK fusion was detected.

Can I request a mutation test?

A mutation test should be performed today in any patient with advanced NSCLC and a non-squamous cell carcinoma (eg, adenocarcinoma) before the therapy is decided. If there are any doubts, it is recommended to ask for a second opinion .

A tissue sample is required for the mutation test. Since this is obtained in the context of a bronchoscopy, the physician can direct the analysis of the mutation status directly. The mutation test is a cash register and takes about 7 to 10 days in the molecular pathological laboratory. The result should be available no later than 10 days. In Germany there are numerous laboratories, which undergo a constant quality control. Ultimately, the result helps the doctor to decide whether a targeted therapy can be used in the patient or if a chemotherapy helps him better.

How does the development continue?

Targeted therapies can not cure lung cancer but positively influence the course of the disease. Patients with EGFR mutations or ALK fusions are only about 15 percent of all lung cancer patients. However, in the case of 52,000 new cases of lung cancer every year, this means several thousand patients, with whom the new therapies can be used. In addition, there are indications that they have a longer life expectancy.

EGFR mutation and ALK fusion are just two examples of how to develop specific, tumor-specific therapies. Numerous other mutations are known, which are known to be involved in the development of lung cancer. How exactly they are created is currently unclear. But if you were to find suitable medications that work precisely on these mutations, you could help other lung cancer patients. Researchers are already working feverishly to develop suitable drugs . Until a drug is adequately tested and marketed, however, up to 10 years may pass.

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