Targeted Molecular Therapy of GBM
Targeted Molecular Therapy of GBM
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DOI：
10.1111/j.1750-3639.2003.tb00006.x
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发表时间：
2003-01
期刊：
影响因子：
6.4
通讯作者：
P. Mischel;T. Cloughesy
中科院分区：
文献类型：
--
作者：
P. Mischel;T. Cloughesy
分子生物学、细胞生物学和基因组学的重大进展大大提高了我们对癌症的认识。现在，这些进步正在转化为治疗。针对特定分子改变的靶向治疗已经在癌症患者的治疗中产生了转变。胶质母细胞瘤（GBM）是成人最常见的脑癌，非常适合这种新方法。GBM通常过表达癌基因EGFR和PDGFR，并且含有肿瘤抑制基因PTEN和TP 53的突变和缺失。这些改变中的一些导致PI 3 K/Akt和Ras/MAPK通路的激活，这为治疗提供了靶点。在本文中，我们审查的方式，分子治疗正在应用于GBM患者，并描述了这些方法的工具：通路抑制剂，单克隆抗体和溶瘤病毒。我们描述的战略是：i）靶向细胞表面上的EGFR、其配体非依赖性变体EGFRvIII和PDGFR，ii）抑制组成性激活的RAS/MAPK和PI 3 K/Akt信号通路，iii）靶向TP 53突变型肿瘤，和iv）阻断GBM血管生成和侵袭。这些新方法可能会彻底改变GBM患者的治疗。它们也将为神经病理学带来新的挑战和机遇。
Major advances in molecular biology, cellular biology and genomics have substantially improved our understanding of cancer. Now, these advances are being translated into therapy. Targeted therapy directed at specific molecular alterations is already creating a shift in the treatment of cancer patients. Glioblastoma (GBM), the most common brain cancer of adults, is highly suited for this new approach. GBMs commonly overexpress the oncogenes EGFR and PDGFR, and contain mutations and deletions of tumor suppressor genes PTEN and TP53. Some of these alterations lead to activation of the PI3K/Akt and Ras/MAPK pathways, which provide targets for therapy. In this paper, we review the ways in which molecular therapies are being applied to GBM patients, and describe the tools of these approaches: pathway inhibitors, monoclonal antibodies and oncolytic viruses. We describe strategies to: i) target EGFR, its ligand‐independent variant EGFRvIII, and PDGFR on the cell surface, ii) inhibit constitutively activate RAS/MAPK and PI3K/Akt signaling pathways, iii) target TP53 mutant tumors, and iv) block GBM angiogenesis and invasion. These new approaches are likely to revolutionize the treatment of GBM patients. They will also present new challenges and opportunities for neuropathology.