The proto-oncogenic ALK is a druggable receptor tyrosine kinase for cancer treatment. Two small molecule inhibitors of ALK, crizotinib and ceritinib, have been recently approved for the treatment of metastatic non-small-cell lung cancer, with marked improvement of progression-free survival of patients. Independent case reports also indicate their potential therapeutic activity in other ALK-rearranged cancers. Numerous single-agent and combination therapy trials are ongoing in lung and many other cancers. Results of these trials are greatly anticipated. Here, we summarize our current understanding of ALK signaling, genomic aberrations in cancer and emerging mechanisms of drug resistance. We will also provide a timely review on all ALK inhibitors and their current status of development in clinical settings.
Keywords: ALK alterations; ALK inhibitor; resistance to ALK inhibitor.