.jpg?format=webp&width=780)
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.
Like
Save
Share