Distinct benefit from crizotinib in lung cancer patients carrying distinct ALK translocations: is fluorescent hybridization in situ testing still sufficient to guide clinical decisions?

ALK rearrangements in lung cancer (LC) were discovered in the year 2007 upon the systematic search for novel LC-associated oncogenes (1,2). Fortunately, an experimental MET inhibitor, PF-2341066 (crizotinib), was by then known to have a concurrent ALK-inhibiting activity and its clinical profile was already under phase I evaluation (3-6). It was quickly revealed that the status of ALK, but not MET, is a primary determinant of tumor sensitivity to crizotinib (5), and a number of subsequent studies heralded a real breakthrough in the treatment of ALK-rearranged cancers (6-9).