Effects of tyrosine kinase inhibition on bone metabolism: Untargeted consequences of targeted therapies Journal Article
| Authors: | Aleman, J. O.; Farooki, A.; Girotra, M. |
| Article Title: | Effects of tyrosine kinase inhibition on bone metabolism: Untargeted consequences of targeted therapies |
| Abstract: | Tyrosine kinase inhibitors (TKIs) are at the forefront of molecular-targeted therapies for cancer. With the advent of imatinib for the treatment of chronic myelogenous leukemia, a new wave of small-molecule therapeutics redefined the oncologic treatment to become chronically administered medications with tolerable side-effect profiles compared with cytotoxic agents. Effects on bone mineral metabolism were observed during early imatinib treatment, in the form of hypophosphatemia with increased urinary phosphorus excretion. This finding led to detailed investigations of off-target effects responsible for changes in bone cell maturation, activity, and impact on bone mass. Subsequently, another BCR-Abl inhibitor (dasatinib), vascular endothelial growth factor (VEGF) inhibitors (sorafenib and sunitinib) as well as rearranged during transfection (RET) inhibitors (vandetanib and cabozantinib) were developed. Inhibition of bone resorption appears to be a class effect and is likely contributed by TKI effects on the hematopoietic and mesenchymal stem cells. As long-term, prospective, clinical outcomes data accumulate on these targeted therapies, the full extent of off-target side effects on bone health will need to be considered along with the significant benefits of tyrosine kinase inhibition in oncologic treatment. © 2014 Society for Endocrinology. |
| Keywords: | osteosarcoma; platelet derived growth factor; vasculotropin; osteolysis; unclassified drug; review; sorafenib; sunitinib; advanced cancer; hypophosphatemia; liver cell carcinoma; nonhuman; solid tumor; bone metastasis; gastrointestinal stromal tumor; imatinib; metastasis; enzyme inhibition; multiple cycle treatment; cell maturation; qt prolongation; calcium; drug effect; enzyme activity; dasatinib; protein tyrosine kinase; chronic myeloid leukemia; vasculotropin inhibitor; kidney carcinoma; protein tyrosine kinase inhibitor; drug mechanism; tyrosine kinase receptor; vandetanib; bone; hyperparathyroidism; mesenchymal stem cell; thyroid carcinoma; bone mass; osteoclast; osteoporosis; hematopoietic stem cell; bcr abl protein; tyrosine kinase inhibitor; absence of side effects; parathyroid hormone; cell activity; osteoblast; colony stimulating factor 1; hypocalcemia; castration resistant prostate cancer; bone metabolism; thyroid medullary carcinoma; molecularly targeted therapy; denosumab; jaw osteonecrosis; torsade des pointes; oncogene ret; pancreatic neuroendocrine tumor; fanconi renotubular syndrome; bone mineral; cabozantinib; secondary hyperparathyroidism; phosphaturia; phosphate metabolism; human; bcr abl protein inhibitor; rearranged during transfection inhibitor; ret kinase; saracatanib; sarcopenia |
| Journal Title: | Endocrine-Related Cancer |
| Volume: | 21 |
| Issue: | 3 |
| ISSN: | 1351-0088 |
| Publisher: | Bioscientifica Ltd |
| Date Published: | 2014-06-01 |
| Start Page: | R247 |
| End Page: | R259 |
| Language: | English |
| DOI: | 10.1530/erc-12-0400 |
| PROVIDER: | scopus |
| PUBMED: | 24478055 |
| DOI/URL: | |
| Notes: | Export Date: 1 August 2014 -- CODEN: ERCAE -- Source: Scopus |
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