24
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Receptor tyrosine kinases: Characterisation, mechanism of action and therapeutic interests for bone cancers

      review-article

      Read this article at

      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Bone cancers are characterised by the development of tumour cells in bone sites, associated with a dysregulation of their environment. In the last two decades, numerous therapeutic strategies have been developed to target the cancer cells or tumour niche. As the crosstalk between these two entities is tightly controlled by the release of polypeptide mediators activating signalling pathways through several receptor tyrosine kinases (RTKs), RTK inhibitors have been designed. These inhibitors have shown exciting clinical impacts, such as imatinib mesylate, which has become a reference treatment for chronic myeloid leukaemia and gastrointestinal tumours. The present review gives an overview of the main molecular and functional characteristics of RTKs, and focuses on the clinical applications that are envisaged and already assessed for the treatment of bone sarcomas and bone metastases.

          Related collections

          Most cited references133

          • Record: found
          • Abstract: found
          • Article: not found

          Oncogenic kinase signalling.

          Protein-tyrosine kinases (PTKs) are important regulators of intracellular signal-transduction pathways mediating development and multicellular communication in metazoans. Their activity is normally tightly controlled and regulated. Perturbation of PTK signalling by mutations and other genetic alterations results in deregulated kinase activity and malignant transformation. The lipid kinase phosphoinositide 3-OH kinase (PI(3)K) and some of its downstream targets, such as the protein-serine/threonine kinases Akt and p70 S6 kinase (p70S6K), are crucial effectors in oncogenic PTK signalling. This review emphasizes how oncogenic conversion of protein kinases results from perturbation of the normal autoinhibitory constraints on kinase activity and provides an update on our knowledge about the role of deregulated PI(3)K/Akt and mammalian target of rapamycin/p70S6K signalling in human malignancies.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Coupling the activities of bone formation and resorption: a multitude of signals within the basic multicellular unit.

            Coupling between bone formation and bone resorption refers to the process within basic multicellular units in which resorption by osteoclasts is met by the generation of osteoblasts from precursors, and their bone-forming activity, which needs to be sufficient to replace the bone lost. There are many sources of activities that contribute to coupling at remodeling sites, including growth factors released from the matrix, soluble and membrane products of osteoclasts and their precursors, signals from osteocytes and from immune cells and signaling taking place within the osteoblast lineage. Coupling is therefore a process that involves the interaction of a wide range of cell types and control mechanisms. As bone remodeling occurs at many sites asynchronously throughout the skeleton, locally generated activities comprise very important control mechanisms. In this review, we explore the potential roles of a number of these factors, including sphingosine-1-phosphate, semaphorins, ephrins, interleukin-6 (IL-6) family cytokines and marrow-derived factors. Their interactions achieve the essential tight control of coupling within individual remodeling units that is required for control of skeletal mass.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              The protein tyrosine kinase family of the human genome.

              As the sequencing of the human genome is completed by the Human Genome Project, the analysis of this rich source of information will illuminate many areas in medicine and biology. The protein tyrosine kinases are a large multigene family with particular relevance to many human diseases, including cancer. A search of the human genome for tyrosine kinase coding elements identified several novel genes and enabled the creation of a nonredundant catalog of tyrosine kinase genes. Ninety unique kinase genes can be identified in the human genome, along with five pseudogenes. Of the 90 tyrosine kinases, 58 are receptor type, distributed into 20 subfamilies. The 32 nonreceptor tyrosine kinases can be placed in 10 subfamilies. Additionally, mouse orthologs can be identified for nearly all the human tyrosine kinases. The completion of the human tyrosine kinase family tree provides a framework for further advances in biomedical science.
                Bookmark

                Author and article information

                Contributors
                Journal
                J Bone Oncol
                J Bone Oncol
                Journal of Bone Oncology
                Elsevier
                2212-1366
                2212-1374
                23 January 2015
                March 2015
                23 January 2015
                : 4
                : 1
                : 1-12
                Affiliations
                [a ]INSERM, UMR 957, Equipe LIGUE Nationale Contre le Cancer 2012, Nantes 44035, France
                [b ]Université de Nantes, Nantes atlantique universités, Pathophysiology of Bone Resorption and Therapy of Primary Bone Tumours, Nantes, France
                [c ]CHU de Nantes, France
                Author notes
                [* ]Corresponding author at: INSERM UMR957, Faculty of Medicine, 1 rue Gaston Veil, 44025 Nantes cedex 1, France. Tel.: +33 240 412 845; fax: +33 240 412 860. dominique.heymann@ 123456univ-nantes.fr
                Article
                S2212-1374(15)20018-8
                10.1016/j.jbo.2015.01.001
                4620971
                26579483
                112fe512-4661-457a-ad61-f749f533f9b8
                © 2015 The Authors

                This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

                History
                : 15 January 2015
                : 18 January 2015
                Categories
                Review Article

                bone metastasis,bone sarcoma,receptor tyrosine kinase,growth factor,inhibitor,therapy

                Comments

                Comment on this article