Abstract

Non-small cell lung cancer (NSCLC) kills more people globally than any other type of cancer. Although histological distinctions between subtypes of NSCLC have long been known, relevant molecular distinctions have only been described within the last few years. ALK gene rearrangements were described in approximately 4% of adenocarcinoma of the lung in 2007. At the same time, by chance, an experimental ALK inhibitor, crizotinib, was also available in Phase I clinical trials. Adopting a novel approach of prescreening patients for evidence of ALK activation to enroll into an expanded cohort of this Phase I study began in late 2008. The dramatic activity of the drug in this molecularly defined subtype of NSCLC lead to the US FDA granting accelerated approval of crizotinib for the treatment of ALK positive NSCLC in August 2011, making it one of the fastest licensed oncology drugs. Given that molecular profiling is increasingly subdividing common cancers, distinct ‘new’ diseases are now being revealed ready to be chacterized by modern oncologists. The implications of the crizotinib example for oncology drug development and recent breakthroughs in our understanding of ALK positive lung cancer’s unique biology, treatment effects and resistance to both standard and experimental therapies will be discussed.