Department of Neurology, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, USA.
Target Oncol. 2010 Sep;5(3):193-200. doi: 10.1007/s11523-010-0160-7. Epub 2010 Sep 16.
Malignant gliomas are a heterogeneous group of tumors with a varying natural history and response to treatment. Despite current therapeutic strategies, these tumors almost universally recur after excision and are associated with a poor survival. Increasingly, the true heterogeneity of these tumors is being correlated with distinct molecular subgroups. Platelet-derived growth factor receptor (PDGFR) alpha is almost universally expressed on glioma cells; expression of the proto-oncogene c-KIT has also been reported. These findings have led to the clinical investigation of inhibitors of this pathway, such as imatinib and dasatinib, for the treatment of recurrent malignant glioma. To date, this approach in unselected patients has been disappointing. However, isolated responses have been seen, which may correlate with constitutive activation of one or more of the corresponding tyrosine kinases. In the future, it is hoped that an increasing knowledge of glioma biology will translate into the more judicious use of these and other targeted therapies, resulting in improvements in patient outcomes. This review describes the preclinical science behind PDGFR and c-KIT, the clinical importance of these molecular pathways and the available data from translational clinical trials.
恶性胶质瘤是一组具有不同自然史和治疗反应的异质性肿瘤。尽管目前有治疗策略，但这些肿瘤在切除后几乎普遍复发，且生存率较差。越来越多的证据表明，这些肿瘤的真正异质性与不同的分子亚群相关。血小板衍生生长因子受体（PDGFR）α几乎普遍存在于胶质瘤细胞上；原癌基因 c-KIT 的表达也有报道。这些发现导致了对该途径抑制剂的临床研究，如伊马替尼和达沙替尼，用于治疗复发性恶性胶质瘤。迄今为止，这种方法在未选择的患者中令人失望。然而，已经观察到孤立的反应，这可能与一个或多个相应的酪氨酸激酶的组成性激活相关。在未来，希望对胶质瘤生物学的了解不断增加将转化为更明智地使用这些和其他靶向治疗，从而改善患者的预后。本文综述了 PDGFR 和 c-KIT 的临床前科学、这些分子途径的临床重要性以及转化临床试验的现有数据。
