Inhibition of c-fms by imatinib - Expanding the spectrum of treatment
Inhibition of c-fms by imatinib - Expanding the spectrum of treatment
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DOI：
10.4161/cc.4.7.1788
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发表时间：
2005-07-01
期刊：
影响因子：
4.3
通讯作者：
Lyons, AB
中科院分区：
文献类型：
--
作者：
Dewar, AL;Zannettino, ACW;Lyons, AB
伊马替尼是一种选择性蛋白酪氨酸激酶抑制剂，目前用于治疗慢性粒细胞白血病（CML）。它通过阻断 bcr-abl 激酶结构域的 ATP 结合位点，特异性抑制表达 bcr-abl 的 CML 祖细胞的生长。伊马替尼还抑制 c-abl、血小板衍生生长因子受体 (PDGFR)、abl 相关基因和干细胞因子受体、c-kit、蛋白酪氨酸激酶。正是通过抑制c-kit，伊马替尼在临床上也用于治疗胃肠道间质瘤。我们最近证明，伊马替尼在治疗浓度下还特异性靶向巨噬细胞集落刺激因子受体 c-fms。尽管这一发现对于目前接受伊马替尼治疗的患者的潜在副作用具有重要意义，但这些结果表明伊马替尼也可能有助于治疗涉及 c-fms 的疾病。这包括乳腺癌和卵巢癌以及类风湿性关节炎等炎症性疾病。我们还推测伊马替尼可用于因破骨细胞活性过度而导致骨破坏的疾病，例如血液系统恶性肿瘤、多发性骨髓瘤。
Imatinib is a selective protein tyrosine kinase inhibitor currently used in the treatment of chronic myeloid leukaemia (CML). It specifically suppresses the growth of bcr-abl expressing CML progenitor cells by blocking the ATP-binding site of the kinase domain of bcr-abl. Imatinib also inhibits the c-abl, platelet derived growth factor receptor ( PDGFR), abl-related gene and stem cell factor receptor, c-kit, protein tyrosine kinases. It is through inhibition of c-kit that imatinib is also used clinically in the treatment of gastrointestinal stromal tumours. We have recently demonstrated that imatinib also specifically targets the macrophage colony stimulating factor receptor, c-fms, at therapeutic concentrations. Although this finding has important implications with regard to potential side effects in patients currently receiving imatinib therapy, these results suggest that imatinib may also be useful in the treatment of diseases where c-fms is implicated. This includes breast and ovarian cancer and inflammatory conditions such as rheumatoid arthritis. We also speculate that imatinib may be used in diseases where bone destruction occurs due to excessive osteoclast activity, such as in the haematologic malignancy, multiple myeloma.