Time filter

Source Type

Pizzi M.,University of Padua | Pizzi M.,New York Medical College | Gaudiano M.,New York Medical College | Todaro M.,New York Medical College | And 5 more authors.
Frontiers in Bioscience - Scholar | Year: 2015

The discovery of Anaplastic Lymphoma Kinase (ALK) by Stephan Morris and colleagues twenty years ago has led to an unprecedented opportunity and provided the basis for a novel and clinically powerful stratification of human cancers. The molecular and biological characterization of ALK and the recognition of alternative mechanisms of activation of the tyrosine kinase receptors have then set the basis for the development and the subsequent application of selective small molecules. These achievements have fostered a new era in oncology, and the result of this new avenue has drastically changed the expectation of many cancer patients. Here we review the mechanisms of ALK activation and the modalities that drive ALK pathogenesis. © 2015, Frontiers in Bioscience. All rights reserved.

Bergalet J.,Institute Of Recherches Cliniques Of Montreal Ircm | Fawal M.,Spanish National Cancer Research Center | Morello D.,University Paul Sabatier | Espinos E.,French Institute of Health and Medical Research | And 3 more authors.
Frontiers in Bioscience - Landmark | Year: 2015

Extensive research has been carried out in the past two decades to provide insights into the molecular mechanisms by which the Nucleophosmin-Anaplastic Lymphoma Kinase (NPM-ALK) exerts its oncogenic effects. These studies led to the concept that NPM-ALK acts at the transcriptional level through the activation of several transcription factors downstream of many different signaling pathways including JAK3/STAT3, PI3K/AKT and RAS/ERK. Nevertheless, the discovery of several RNA-binding proteins (RBPs) within ALK interactome suggested an additional and complementary role of this oncogenic kinase at the post-transcriptional level. This review gives emerging views in ALK-mediated post-transcriptional regulation with a focus on RBPs that are associated with ALK. We will summarize the capacity of NPM-ALK in modulating the biological properties of RBPs and then discuss the role of cytoplasmic aggregates, called AGs for "ALK granules", which are observed in anaplastic large cell lymphoma (ALCL) expressing the ALK kinase. AGs contain polyadenylated mRNAs and numerous RBPs but are distinct from processing bodies (PBs) and stress granules (SGs), two well-known discrete cytoplasmic sites involved in mRNA fate.

Bonzheim I.,University of Tubingen | Steinhilber J.,University of Tubingen | Fend F.,University of Tubingen | Quintanilla-Martinez L.,University of Tubingen | Quintanilla-Martinez L.,European Research Initiative on ALK related Malignancies ERIA
Frontiers in Bioscience - Scholar | Year: 2015

The current classification of lymphoid neoplasms is based on the integrated utilisation of morphological, immunohistochemical, genetic and clinical criteria to define disease entities. Anaplastic large cell lymphoma is a paradigm for the identification of a disease entity based on morphological observations and immunophenotype, which paved the way for the subsequent discovery of the characteristic cytogenetic abnormality the translocation t(2;5) (p23;q35). In 1994, the t(2;5) was cloned and the NPM-ALK fusion gene generated by this rearrangement was identified. The year 2014 marked the 20thanniversary of this seminal publication by Steve Morris et al. The discovery of anaplastic lymphoma kinase (ALK) has allowed the definition of a distinct entity within the clinically and pathologically heterogeneous group of CD30+ lymphomas. The diagnosis of ALK-positive ALCL has become straightforward due to the generation of the reliable monoclonal antibody ALK-1 that also has led to the recognition of the histologic spectrum of the disease. ALK-positive ALCL has evolved in the last 20 years to an exciting model for signal transduction studies and targeted therapy. © 1996-2015.

Voena C.,University of Turin | Voena C.,Center for Experimental Research and Medical Studies | Voena C.,Harvard University | Peola S.,University of Turin | And 5 more authors.
Frontiers in Bioscience - Scholar | Year: 2015

Twenty years ago anaplastic lymphoma kinase (ALK) was discovered in anaplastic large cell lymphoma (ALCL), but the interest in ALK as an oncogene grew only in recent years when ALK rearrangements were reported as recurrent genetic lesions in lung carcinoma and activating single point mutations were described in neuroblastoma. In this review we will describe the main features of ALK-rearranged solid tumors, with particular emphasis to NSCLC and neuroblastoma. We will discuss the numerous in vitro and in vivo studies that confirmed ALK as the "driver" oncogene in these tumors and the achievements in clinical settings with ALK inhibitors that validated ALK as a therapeutic target. We will finally end with the description of putative innovative therapeutic approaches that are on going to overcome acquired resistance that invariably occurs in crizotinib treated NSCLC patients or intrinsic resistance to crizotinb therapy reported in neuroblastoma. © 1996-2015.

Giuriato S.,French Institute of Health and Medical Research | Giuriato S.,University Paul Sabatier | Giuriato S.,French National Center for Scientific Research | Giuriato S.,European Research Initiative on ALK related Malignancies ERIA | And 2 more authors.
Frontiers in Bioscience - Scholar | Year: 2015

Our current understanding of oncogenic Anaplastic Lymphoma Kinase (ALK)-induced lymphomagenesis has relied for over 20 years on multiple and complementary studies performed on various experimental models, encompassing ALK oncogene expressing cells, their grafts into immune-compromised mice, the generation of genetically engineered mouse models (GEMMs) and, when available, the use of patient samples from Anaplastic Large Cell Lymphoma (ALCL) tumour banks. Of note, and to our knowledge, no ALK-positive ALCL 3D culture system has been described so far. In this review, we will first outline how these different cell and mouse models were designed, and what key findings they revealed (or confirmed) towards oncogenic ALK-induced lymphomagenesis. Secondly, we will discuss how recent and revolutionary advances in genetic engineering technology are likely to complete our understanding of ALK-related diseases in an effort to improve current therapeutic approaches. © 2015, Frontiers in Bioscience. All rights reserved.

Discover hidden collaborations