Expert opinion on investigational drugs
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Anaplastic lymphoma kinase (ALK) is a receptor tyrosine kinase normally expressed in the developing nervous tissue. Genetic alterations of ALK are associated with a number of cancers, including anaplastic large cell lymphoma (ALCL) and a subset of non-small cell lung cancer (NSCLC). Standard therapies for these diseases include surgery plus unspecific cytotoxic agents, with a low therapeutic window and significant treatment-associated systemic toxicity. A few small-molecule inhibitors of ALK kinase activity have been described in the recent years, some of which are currently undergoing clinical evaluation. ⋯ Understanding the specific genetic aberration that causes cancer development and progression allows major advances in cancer therapy. Along the same way shown by imatinib in chronic myeloid leukemia, compounds that selectively target ALK are bringing a revolution in the treatment of ALK-positive tumors. Crizotinib has just been approved, and new more potent ALK inhibitors will shortly follow. These molecules represent another excellent proof-of-principle for targeted therapy.