Dysregulation of bone remodelling by imatinib mesylate Export

@article{citeulike:6079757, abstract = {Imatinib mesylate is a rationally designed tyrosine kinase inhibitor that has revolutionised the treatment of chronic myeloid leukaemia and gastro-intestinal stromal tumours. Although the efficacy and tolerability of imatinib is a vast improvement over conventional chemotherapies, the drug exhibits off-target effects. An unanticipated side-effect of imatinib therapy is hypophosphataemia and hypocalcaemia, which in part has been attributed to drug-mediated changes to renal and gastro-intestinal handling of phosphate and calcium. However, emerging data suggests that imatinib also targets cells of the skeleton, stimulating the retention and sequestration of calcium and phosphate to bone, leading to decreased circulating levels of these minerals. The aim of this review is to highlight our current understanding of the mechanisms surrounding the effects of imatinib on the skeleton. In particular, it examines recent studies which suggest that imatinib has direct effects on bone-resorbing osteoclasts and bone-forming osteoblasts through inhibition of c-fms, c-kit, carbonic anhydrase II and the platelet-derived growth factor receptor. The potential application of imatinib in the treatment of cancer induced osteolysis will also be discussed. 10.1182/blood-2009-08-237404}, author = {Vandyke, Kate and Fitter, Stephen and Dewar, Andrea L. and Hughes, Timothy P. and Zannettino, Andrew C. W.}, citeulike-article-id = {6079757}, citeulike-linkout-0 = {http://dx.doi.org/10.1182/blood-2009-08-237404}, citeulike-linkout-1 = {http://bloodjournal.hematologylibrary.org/content/blood-2009-08-237404v1/.abstract}, citeulike-linkout-2 = {http://bloodjournal.hematologylibrary.org/content/blood-2009-08-237404v1/.full.pdf}, citeulike-linkout-3 = {http://view.ncbi.nlm.nih.gov/pubmed/19890095}, citeulike-linkout-4 = {http://www.hubmed.org/display.cgi?uids=19890095}, day = {4}, doi = {10.1182/blood-2009-08-237404}, journal = {Blood}, keywords = {bone, chemotherapy, leukemia}, month = {November}, pages = {blood-2009-08-237404+}, posted-at = {2009-11-06 02:01:45}, priority = {2}, title = {Dysregulation of bone remodelling by imatinib mesylate}, url = {http://dx.doi.org/10.1182/blood-2009-08-237404}, year = {2009} }

TY - JOUR ID - citeulike:6079757 L3 - citeulike-article-id:6079757 N2 - Imatinib mesylate is a rationally designed tyrosine kinase inhibitor that has revolutionised the treatment of chronic myeloid leukaemia and gastro-intestinal stromal tumours. Although the efficacy and tolerability of imatinib is a vast improvement over conventional chemotherapies, the drug exhibits off-target effects. An unanticipated side-effect of imatinib therapy is hypophosphataemia and hypocalcaemia, which in part has been attributed to drug-mediated changes to renal and gastro-intestinal handling of phosphate and calcium. However, emerging data suggests that imatinib also targets cells of the skeleton, stimulating the retention and sequestration of calcium and phosphate to bone, leading to decreased circulating levels of these minerals. The aim of this review is to highlight our current understanding of the mechanisms surrounding the effects of imatinib on the skeleton. In particular, it examines recent studies which suggest that imatinib has direct effects on bone-resorbing osteoclasts and bone-forming osteoblasts through inhibition of c-fms, c-kit, carbonic anhydrase II and the platelet-derived growth factor receptor. The potential application of imatinib in the treatment of cancer induced osteolysis will also be discussed. 10.1182/blood-2009-08-237404 JF - Blood TI - Dysregulation of bone remodelling by imatinib mesylate SP - blood-2009-08-237404 KW - bone KW - chemotherapy KW - leukemia AU - Vandyke, Kate AU - Fitter, Stephen AU - Dewar, Andrea AU - Hughes, Timothy AU - Zannettino, Andrew PY - 2009/11/04/ UR - http://dx.doi.org/10.1182/blood-2009-08-237404 ER -