11May 2023
EML4‐ALK biology and drug resistance in Non‐Small Cell Lung Cancer

EML4‐ALK biology and drug resistance in Non‐Small Cell Lung Cancer

Anaplastic Lymphoma Kinase (ALK) can become cancerous due to different mutations such as point-mutations or gene fusions. EML4-ALK variants are a result of different breakpoints and form compartments with varying physical properties. Variant 1 has solid-like properties, is more dependent on Hsp90 for stability, and is more sensitive to ALK tyrosine kinase inhibitors (TKIs) than Variant 3. Patients with Variant 3 have a worse prognosis and higher metastatic risk. Latest generation ALK-TKIs are helpful for most patients with EML4-ALK fusions, but resistance can occur via point-mutations like G1202R. This article discusses the biology of EML4-ALK variants, their impact on treatment response, ALK-TKI drug resistance mechanisms, and potential combination therapies.

  • #oncology

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