Three articles in this issue of the Journal report on the therapeutic potential of a new kid on the kinase inhibitor block: crizotinib, an ATP-competitive inhibitor of the anaplastic lymphoma kinase (ALK) receptor tyrosine kinase. Kwak et al.1 summarize a study involving patients with non–small-cell lung cancer who were enrolled in a phase 1 trial, starting in 2008, hot on the heels of a study ...

Aberrant protein kinase activity promotes tumor survival and proliferation, and targeted kinase inhibitors that halt growth and promote apoptosis demonstrate some cancers are truly kinase addicted. Clinically, this is best exemplified by chronic myeloid leukemia (CML), driven by the fusion kinase BCR-ABL, where tyrosine kinase inhibitor (TKI) therapy can control the disease for years, perhaps i...

The identification of echinoderm microtubule-associated protein-like 4 (EML4) and anaplastic lymphoma kinase (ALK) fusion gene in non-small cell lung cancer (NSCLC) has radically changed the treatment of a subset of patients harboring this oncogenic driver. Crizotinib was the first ALK tyrosine kinase inhibitor to receive fast approval and is currently indicated as the first-line therapy for ad...

PURPOSE We investigated the incidence of concomitant epidermal growth factor receptor (EGFR) mutations and anaplastic lymphoma kinase (ALK) rearrangements in Chinese patients with non-small cell lung cancer (NSCLC), and assessed responses to EGFR tyrosine kinase inhibitors (EGFR-TKIs) and crizotinib in such tumors. EXPERIMENTAL DESIGN We screened 977 consecutive patients with NSCLC for the pr...

The genetic landscape of medullary thyroid cancer (MTC) is not yet fully understood, although some oncogenic mutations have been identified. To explore genetic profiles of MTCs, formalin-fixed, paraffin-embedded tumor tissues from MTC patients were assayed on the Ion AmpliSeq Cancer Panel v2. Eighty-four sporadic MTC samples and 36 paired normal thyroid tissues were successfully sequenced. We d...

Anaplastic lymphoma kinase (ALK) fusion is a common mechanism underlying pathogenesis of non-small cell lung carcinoma (NSCLC) where these rearrangements represent important diagnostic and therapeutic targets. In this study, we found a new ALK fusion gene, SEC31A-ALK, in lung carcinoma from a 53-year-old Korean man. The conjoined region in the fusion transcript was generated by the fusion of SE...

Lung cancer is the leading cause of deaths worldwide, with majority consisting non-small cell lung (NSCLC). Genetic mutations present an opportunity for targeted therapy, in addition to current mainstay treatments such as chemotherapy and radiotherapy. Overall, 5% NSCLCs have anaplastic lymphoma kinase (ALK) mutation, often prevalent a younger population. Crizotinib ALK inhibitor that was appro...

CCAAT/enhancer binding protein beta (C/EBPbeta) is one of a 6-member family of C/EBPs. These transcription factors are involved in the regulation of various aspects of cellular growth and differentiation. Although C/EBPbeta has important functions in B- and T-cell differentiation, its expression has not been well studied in lymphoid tissues. We, therefore, analyzed its expression by immunohisto...

The dual ALK/MET inhibitor crizotinib was recently approved for the treatment of metastatic and late-stage ALKþ NSCLC, and is currently in clinical trial for other ALK-related diseases. As predicted after other tyrosine kinase inhibitors' clinical experience, the first mutations that confer resistance to crizotinib have been described in patients with non–small cell lung cancer (NSCLC) and in o...

Anaplastic large cell lymphoma (ALCL) is a subtype of non-Hodgkin lymphoma composed of CD30-positive cells and now recognized as three different entities: primary cutaneous ALCL, primary systemic anaplastic lymphoma kinase (ALK)-positive (ALK+) ALCL and primary ALK-negative (ALK-) ALCL. ALK+ ALCL is supposed to have a better prognosis than ALK- ALCL. It is rarely metastasized to other sites, es...