New strategies in the molecular targeting of glioblastoma: how do you hit a moving target?
New strategies in the molecular targeting of glioblastoma: how do you hit a moving target?
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DOI：
10.1158/1078-0432.ccr-09-2268
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发表时间：
2011-01-01
期刊：
影响因子：
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通讯作者：
Mischel PS
中科院分区：
文献类型：
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作者：
Cloughesy TF;Mischel PS
癌症是一种分子复杂、基因组不稳定的疾病。耐药突变的选择、反馈环路的激活和串扰通路的上调提供了逃逸路线，癌细胞通过这些逃逸路线维持通过关键下游效应器的信号流，以促进治疗耐药性。因此，针对癌症中的信号转导途径可能需要瞄准“移动目标”。需要预测耐药途径，以指导选择能够产生持久治疗反应的药物。在这篇新策略文章中，我们讨论了癌症的复杂性和“适应性”能力带来的挑战，并提出了潜在的新诊断策略，以便更有效地指导癌症靶向治疗。我们专注于胶质母细胞瘤（GBM），这是成人最常见的恶性原发性脑肿瘤。 GBM 是一种“通路驱动”的分子异质癌症模型，通过癌症基因组图谱获得的新基因组见解已经成熟，可以与功能生物学整合并纳入新的分子诊断测定中。
Cancer is a molecularly complex, genomically unstable disease. Selection for drug resistance mutations, activation of feedback loops and upregulation of cross-talk pathways provide escape routes by which cancer cells maintain signal flux through critical downstream effectors to promote therapeutic resistance. Targeting signal transduction pathways in cancer may therefore require aiming at a “moving target”. The routes of resistance need to be anticipated to guide the selection of drugs that will lead to durable therapeutic response. In this New Strategies article, we discuss the challenges imposed by the complexity and “adaptive” capacity of cancer and suggest potential new diagnostic strategies in order to more effectively guide targeted cancer therapy. We focus on glioblastoma (GBM), the most common malignant primary brain tumor of adults. GBM is a model for a “pathway-driven”, molecularly heterogeneous cancer for which new genomic insights obtained through The Cancer Genome Atlas are ripe for integration with functional biology and incorporation into new molecular diagnostic assays.