Lung adenocarcinoma is the most common form of lung cancer. It develops from glandular cells that line the alveoli and produce mucus or other substances. In around five percent of patients, a genetic alteration is present: the fusion of the EML4 and ALK genes. This fusion can occur in different variants, each influencing tumor growth in distinct ways.
Until now, patients with EML4-ALK fusions were treated the same way, regardless of the specific variant. A recent study shows that these differences can play a critical role in disease progression and response to therapy.
Researchers at the German Cancer Research Center (DKFZ), together with colleagues from Stanford University, demonstrated that the two most common variants behave very differently: variant V3 produces more aggressive tumors than variant V1 and responds less effectively to certain targeted drugs (ALK inhibitors).
Analysis of the largest dataset of patients with EML4-ALK-positive lung cancer to date confirmed these findings: different variants often co-occurred with distinct additional genetic alterations, further affecting disease course and treatment response.
“Our results show that not all ALK fusions are the same,” says DZL researcher Rocío Sotillo from the DKFZ. “Knowing the specific variant could help tailor treatments more precisely to each patient in the future.”
The study highlights that a more differentiated consideration of genetic driver mutations may become an important key for personalized lung cancer therapy.
The work was supported by the German Center for Lung Research (DZL), Worldwide Cancer Research, and the National Institutes of Health.
