The treatment of advanced non-small-cell lung cancer with anaplastic lymphoma kinase genetic alterations: reality and hopes

Author(s): Assunta Sgambato, Francesca Casaluce, Antonio Rossi, Paolo Maione, Paola Claudia Sacco, Fortunato Ciardiello & Cesare Gridelli

Targeted therapies based on molecular diagnostics have opened a new era of personalized medicine in lung cancer treatment. Recently, anaplastic lymphoma kinase (ALK) fusion gene emerged as an important biomarker for identifying a small proportion of non-small-cell lung cancer (NSCLC) patients that will benefit from ALK kinase inhibitor crizotinib, like EGFR activating mutations and EGFR tyrosine kinase inhibitors. Despite the remarkable initial responses, acquired resistance to crizotinib develops within a year and promising second generation of ALK inhibitors are in current development to overcome it. This review will focus on the basic molecular pathology of ALK gene rearrangement in NSCLC, current testing methods, treatment strategies against ALK-positive and crizotinib-resistant NSCLCs.