ALK: a tyrosine kinase target for cancer therapy.

The anaplastic lymphoma kinase () gene plays an important physiologic role in the development of the brain and can be oncogenically altered in several malignancies, including non-small-cell lung cancer (NSCLC) and anaplastic large cell lymphomas (ALCL). Most prevalent alterations are chromosomal rearrangements resulting in fusion genes, as seen in ALCL and NSCLC. In other tumors, copy-number gains and activating mutations have been described. Dramatic and often prolonged responses are seen in patients with alterations when treated with ALK inhibitors. Three of these-crizotinib, ceritinib, and alectinib-are now FDA approved for the treatment of metastatic NSCLC positive for fusions. However, the emergence of resistance is universal. Newer ALK inhibitors and other targeting strategies are being developed to counteract the newly emergent mechanism(s) of ALK inhibitor resistance. This review outlines the recent developments in our understanding and treatment of tumors with alterations.