Departments of Neurosurgery, Johns Hopkins University School of Medicine, CRB II Rm. 257, 1550 Orleans Street, Baltimore, MD 21231, USA.
Trends Mol Med. 2011 Jun;17(6):301-312. doi: 10.1016/j.molmed.2011.01.011. Epub 2011 Mar 14.
Despite advances in treatment for glioblastoma multiforme (GBM), patient prognosis remains poor. Although there is growing evidence that molecular targeting could translate into better survival for GBM, current clinical data show limited impact on survival. Recent progress in GBM genomics implicate several activated pathways and numerous mutated genes. This molecular diversity can partially explain therapeutic resistance and several approaches have been postulated to target molecular changes. Furthermore, most drugs are unable to reach effective concentrations within the tumor owing to elevated intratumoral pressure, restrictive vasculature and other limiting factors. Here, we describe the preclinical and clinical developments in treatment strategies of GBM. We review the current clinical trials for GBM and discuss the challenges and future directions of targeted therapies.
尽管胶质母细胞瘤(GBM)的治疗取得了进展,但患者的预后仍然很差。尽管越来越多的证据表明分子靶向治疗可能会改善 GBM 的生存,但目前的临床数据显示对生存的影响有限。GBM 基因组学的最新进展提示了几个激活的通路和许多突变基因。这种分子多样性部分解释了治疗耐药性,并且已经提出了几种方法来针对分子变化。此外,由于肿瘤内压力升高、血管受限和其他限制因素,大多数药物无法在肿瘤内达到有效浓度。在这里,我们描述了 GBM 治疗策略的临床前和临床进展。我们回顾了目前针对 GBM 的临床试验,并讨论了靶向治疗的挑战和未来方向。