New Strategies for Treatment of ALK Rearranged Non-Small Cell Lung Cancers
Cet article passe en revue les travaux récents sur les mécanismes de résistance au crizotinib dans les cancers du poumon non à petites cellules avec réarrangements du gène ALK
The identification of oncogenic alterations in subsets of non-small cell lung cancers (NSCLC) is transforming clinical care. Genomic rearrangements in the anaplastic lymphoma kinase (ALK) are detected in 3 to 7% of NSCLC patients. The ALK tyrosine kinase inhibitor crizotinib has demonstrated clinical efficacy in ALK rearranged NSCLC patients and was recently approved by the FDA. Crizotinib is currently under additional phase III clinical development as both initial and second line therapy for advanced ALK rearranged NSCLC. However new challenges in the diagnosis and treatment of this subset of NSCLC have emerged. These include the most effective means of diagnosing ALK rearranged NSCLC and the emergence of acquired drug resistance to crizotinib. In this review we will review current treatment and diagnosis as well as the present knowledge on acquired resistance mechanisms to crizotinib and discuss the strategies presently underway to clinically overcome acquired drug resistance.