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|Ref Type||Journal Article|
|Authors||Solomon B, Wilner KD, Shaw AT|
|Title||Current status of targeted therapy for anaplastic lymphoma kinase-rearranged non-small cell lung cancer.|
|Journal||Clinical pharmacology and therapeutics|
|Abstract Text||The identification of chromosomal rearrangements involving the anaplastic lymphoma kinase (ALK) gene in ~3-5% of non-small cell lung cancer (NSCLC) tissues and the demonstration that the first-in-class ALK tyrosine kinase inhibitor, crizotinib, can effectively target these tumors represent a significant advance in the evolution of personalized medicine for NSCLC. Single-arm studies demonstrating rapid and durable responses in the majority of ALK-positive NSCLC patients treated with crizotinib have been followed by a randomized phase III clinical trial in which superiority of crizotinib over chemotherapy was seen in previously treated ALK-positive NSCLC patients. However, despite the initial responses, most patients develop acquired resistance to crizotinib. Several novel therapeutic approaches targeting ALK-positive NSCLC are currently under evaluation in clinical trials, including second-generation ALK inhibitors, such as LDK378, CH5424802 (RO5424802802), and AP26113, and heat shock protein 90 inhibitors.|
|Molecular Profile||Treatment Approach|
|Gene Name||Source||Synonyms||Protein Domains||Gene Description||Gene Role|
|Drug Name||Trade Name||Synonyms||Drug Classes||Drug Description|
|Gene||Variant||Impact||Protein Effect||Variant Description||Associated with drug Resistance|
|Molecular Profile||Indication/Tumor Type||Response Type||Therapy Name||Approval Status||Evidence Type||Efficacy Evidence||References|
|ALK fusion||lung non-small cell carcinoma||sensitive||Brigatinib||Phase Ib/II||Actionable||In a phase I/II clinical trial, Alunbrig (brigatinib) was determined to be safe and efficacious in patients with advanced, ALK-fusion positive NSCLC (PMID: 24091716).||24091716|