Targeting oncogenic BRAF in human cancer.
Targeting oncogenic BRAF in human cancer.
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DOI：
10.1007/82_2011_162
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发表时间：
2012
影响因子：
--
通讯作者：
Solit, David B.
中科院分区：
文献类型：
--
作者：
Pratilas, Christine A.;Xing, Feng;Solit, David B.
MAPK通路激活是人类癌症中常见的事件，通常是BRAF和RAS癌基因激活突变的结果。BRAF错义激酶结构域突变，绝大多数是V600E，发生在大约8%的人类肿瘤中。这些突变在分布上与RAS突变不重叠，最常见于黑色素瘤，但也见于结肠、甲状腺、肺和其他部位的肿瘤。V600EBRAF可刺激ERK信号，诱导增殖，促进转化，支持其作为癌基因的分类。鉴于BRAF突变在人类癌症中的频繁发生，以及发生突变的肿瘤对BRAF活性的持续需求，开发BRAF靶向抑制剂及其下游效应物的努力正在进行中。与目前可用于由MAPK通路激活突变驱动的肿瘤的全身治疗相比，这些药物提供了更高疗效和更低毒性的可能性。BRAF选择性抑制剂PLX4032和GSK2118436的早期临床结果表明，该策略将在一组由致癌BRAF驱动的肿瘤患者中被证明是成功的。
MAPK pathway activation is a frequent event in human cancer and is often the result of activating mutations in the BRAF and RAS oncogenes. BRAF missense kinase domain mutations, the vast majority of which are V600E, occur in approximately 8% of human tumors. These mutations, which are non-overlapping in distribution with RAS mutations, are observed most frequently in melanoma but also in tumors arising in the colon, thyroid, lung and other sites. Supporting its classification as an oncogene, V600EBRAF stimulates ERK signaling, induces proliferation and is capable of promoting transformation. Given the frequent occurrence of BRAF mutations in human cancer and the continued requirement for BRAF activity in the tumors in which it is mutated, efforts are underway to develop targeted inhibitors of BRAF and its downstream effectors. These agents offer the possibility of greater efficacy and less toxicity than the systemic therapies currently available for tumors driven by activating mutations in the MAPK pathway. Early clinical results with the BRAF-selective inhibitors PLX4032 and GSK2118436 suggest that this strategy will prove successful in a select group of patients whose tumors are driven by oncogenic BRAF.
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影响因子：
64.8
作者：
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通讯作者：
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影响因子：
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作者：
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作者：
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通讯作者：
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影响因子：
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作者：
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