157 ISSN 1758-1966 10.2217/LMT.12.28 © 2012 Future Medicine Ltd Lung Cancer Manage. (2012) 1(3), 157–160 In the last decade a better understanding of tumor biology has led to the identification of several potential oncogenic drivers in non-small-cell lung cancer (NSCLC), including the ALK translocation, described in approximately 6–8% of adeno carcinomas [1]. This was recognized as a potential target early in the clinical development of crizotinib (Xalkori, Pfizer, NY); following clinically significant objective responses seen in two ALK-positive patients treated in a Phase I clinical trial in solid tumors and lymphomas, in which the drug was initially investigated as a c-MET/ HGF tyrosine kinase inhibitor. The study was consequently amended to include an expanded cohort of ALK-positive patients with lung cancer [2]. Accelerated US FDA approval of crizotinib in advanced NSCLC patients with ALK translocation, as identified by Vysis (Abbott Moleular) ALK break apart FISH probe kit, has been recently granted, for the first time in NSCLC, based on the results of Phase I and II trial data (PROFILE 1005, NCT00932451). The overall response rate was 61% in the Phase I portion of the study and 51% from the preliminary analysis of the Phase II trial, progression-free survival in Phase I was 10 months with an early and prolonged clinical benefit and a tolerable safety profile [3–6]. Besides this shining and very rapid ascent in the scientific scenario, there are still some noteworthy issues that should be pointed out. To select candidate patients to receive crizotinib, the FDA has established FISH as the gold standard for detecting ALK rearrangements. However, other methods such as immunohistochemistry (IHC) and reverse transcriptase-PCR (RT-PCR), have been evaluated. The ALK FISH technique is cumbersome, may be associated with false negatives (splitting of red and green signals can be subtle), requires specialized technical resources and expertise, is not available or reproducible in all pathology laboratories and the cost per patient is still high [7]. IHC is widely used, rapid and the pathologist-preferred method for screening and diagnosis. The first major limitation to routine use of IHC to detect ALK rearrangement is the often lowlevel expression of ALK fusion proteins in positive NSCLC cases, which needs the development of more sensitive IHC methods and different antibodies. Several