The therapeutic potential of anaplastic lymphoma kinase inhibitors in lung cancer: rationale and clinical evidence

Author(s): Andrew J Weickhardt, D Ross Camidge

In the last few years it has been demonstrated that approximately 4% of non-small-cell lung cancer is driven by an ALK gene rearrangement. When such a rearrangement occurs an oncogene addicted state appears to then exist within the cancer cell. Crizotinib, an anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitor, is effective in preclinical models of ALK-rearranged lung cancer, and has demonstrated high response rates in Phase I/II clinical trials in this sub-population. This review summarizes ALK biology, recent developments in techniques for the detection of ALK rearrangements, clinical characteristics of this population and relevant clinical trial results. Following filing for accelerated approval, crizotinib may soon be licensed for the treatment of ALK-positive non-small-cell lung cancer in the USA as well as worldwide.