Feldkamp M M, Lau N, Guha A
Division of Neurosurgery, Toronto Hospital, Ontario, Canada.
J Neurooncol. 1997 Dec;35(3):223-48. doi: 10.1023/a:1005800114912.
Aberrations in a number of signal transduction pathways have been identified as playing a key role in the molecular pathogenesis of astrocytomas and their progression to high grade glioblastoma multiforme (GBM). GBMs are characterized by overexpression of the Platelet Derived Growth Factor Receptors (PDGFR) and their ligands (PDGF), as well as the Epidermal Growth Factor Receptor (EGF-R). These receptors activate the Ras pathway, a key cellular signal transduction pathway, culminating in the activation of a wide range of Ras-dependent cellular events. GBMs have also been found to either overexpression or lose expression of various Protein Kinase C (PKC) isoforms. Major strides are being made in developing pharmacological agents which specifically inhibit these growth factor receptors and intracellular signal transduction pathways. Elucidating the role of these pathways in GBMs is thus of major clinical importance, as these novel molecularly-targeted agents may prove of use in the clinical management of GBMs in the future.
一些信号转导通路的异常已被确定在星形细胞瘤的分子发病机制及其向高级别多形性胶质母细胞瘤（GBM）进展过程中起关键作用。GBM的特征是血小板衍生生长因子受体（PDGFR）及其配体（PDGF）以及表皮生长因子受体（EGF-R）的过度表达。这些受体激活Ras通路，这是一条关键的细胞信号转导通路，最终导致多种Ras依赖性细胞事件的激活。还发现GBM要么过度表达要么失去各种蛋白激酶C（PKC）亚型的表达。在开发特异性抑制这些生长因子受体和细胞内信号转导通路的药物方面正在取得重大进展。因此，阐明这些通路在GBM中的作用具有重要的临床意义，因为这些新型分子靶向药物未来可能被证明可用于GBM的临床管理。
