INTRODUCTION Anaplastic lymphoma kinase (ALK) and ROS1 rearrangements define important molecular subgroups of advanced non-small cell lung cancer (NSCLC). The identification of these genetic driver alterations created new potential for highly active therapeutic interventions. After discovery of ALK rearrangements in NSCLC, it was recognized that these confer sensitivity to ALK inhibition. Areas...

PURPOSE Approximately 5% of lung adenocarcinomas harbor an EML4-ALK gene fusion and define a unique tumor group that may be responsive to targeted therapy. However ALK-rearranged lung adenocarcinomas are difficult to detect by either standard fluorescence in situ hybridization or immunohistochemistry (IHC) assays. In the present study, we used novel antibodies to compare ALK protein expression ...

Anaplastic large-cell lymphomas (ALCLs) carry chromosome translocations in which the anaplastic lymphoma kinase (ALK) gene is fused to several partners, most frequently, the NPM1 gene. We have demonstrated that the constitutive activation of ALK fusion proteins results in cellular transformation and lymphoid neoplasia. Herein, we specifically down-regulated ALK protein expression by using small...

BACKGROUND Since 2007 when anaplastic lymphoma kinase (ALK) rearrangements were discovered in non-small cell lung cancer, the ALK gene has received attention due to ALK-targeted therapy, and a notable treatment advantage has been observed in patients harboring the EML4/ALK translocation. However, using ALK-fluorescence in situ hybridization (FISH) as the standard method has demerits such as hig...

The anaplastic lymphoma kinase (ALK) gene encodes a receptor tyrosine kinase, and many kinds of ALK fusion genes have been found in a variety of carcinomas. There is almost no detectable expression of ALK in adults. However, through ALK gene rearrangement, the resultant ALK fusion protein is aberrantly overexpressed and dimerized through the oligomerization domains, such as the coiled-coil doma...

pose: Anaplastic lymphoma kinase (ALK) fusion genes represent novel oncogenes for non–small ng cancers (NSCLC). Several ALK inhibitors have been developed, and are now being evaluated in ositive NSCLC. The feasibility of detecting ALK fusion genes in samples obtained by endobronchial und-guided transbronchial needle aspiration (EBUS-TBNA) was determined. The clinicopathologic teristics of ALK-p...

PURPOSE The first-generation ALK tyrosine kinase inhibitor (TKI) crizotinib is a standard therapy for patients with ALK-rearranged non-small cell lung cancer (NSCLC). Several next-generation ALK-TKIs have entered the clinic and have shown promising activity in crizotinib-resistant patients. As patients still relapse even on these next-generation ALK-TKIs, we examined mechanisms of resistance to...

Non-small-cell lung cancer (NSCLC) with echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase (EML4-ALK) translocation is resistant to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs), including gefitinib and erlotinib, but responds to the ALK-TKI crizotinib. Characterization of EML4-ALK translocation may provide invaluable information to facilitat...

Anaplastic lymphoma kinase (ALK) is an important drug target in many cancers, including lymphoma, neuroblastoma, and lung cancer. Here, we demonstrate proof-of-principle for a novel and inexpensive assay for ALK inhibitor activity and identification in zebrafish. We demonstrate that the human oncogenic ALK fusion, NPM-ALK, drives overproduction of iridophores, a highly visible, shiny pigment ce...

The oncogenic function of gene translocations involving the anaplastic lymphoma kinase (ALK) was first reported in rare subtypes of non-Hodgkin's lymphoma almost two decades ago. More recently, aberrant ALK signaling was found to be an oncogenic driver in subsets of non-small cell lung cancer (NSCLC), particularly in patients with little or no tobacco smoking history. The advent of molecularly ...