Official websites use. Share sensitive information only on official, secure websites. 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.
To be able to play their physiological role intra- and inter-cellular signal transmission and adaptation to changes in the microenvironment , cells must be able to receive, integrate and respond to numerous extracellular messengers. These communications between cells and their environment are made possible through the attachment of molecules considered as messengers to their receptors, identified as effectors cytokines, growth factors, etc.
Membrane receptors possess i an extracellular hydrophilic domain, often glycosylated, which recognises the ligand; ii a hydrophobic trans-membrane domain that makes embedding possible within the lipid bilayer of the plasma membrane; and iii an intra-cytoplasmic domain dedicated to signal transduction within the cell. The binding of a ligand to its receptor is specific, reversible and involves a large number of low-energy bonds hydrogen, ionic, hydrophobic, and Van der Waals.
Thus, at equilibrium, the dissociation rate is equal to the rate of association. The guanylyl cyclase-coupled receptors include natriuretic peptide, nitric oxide, carbon monoxide and enterotoxin receptors. The binding of the ligand to the extracellular domain of its receptor leads to intracellular activation of the guanylate cyclase domain of the receptor chain, and synthesis of a cyclic GMP for activating the cAMP-dependent protein kinase environment [1]. The G protein-coupled receptors are characterised by seven transmembrane domains.
