Mechanism of MEK inhibition determines efficacy in mutant KRAS- versus BRAF-driven cancers

被引：0

作者：

Georgia Hatzivassiliou

Jacob R. Haling

Huifen Chen

Kyung Song

Steve Price

Robert Heald

Joanne F. M. Hewitt

Mark Zak

Ariana Peck

Christine Orr

Mark Merchant

Klaus P. Hoeflich

Jocelyn Chan

Shiuh-Ming Luoh

Daniel J. Anderson

Mary J. C. Ludlam

Christian Wiesmann

Mark Ultsch

Lori S. Friedman

Shiva Malek

Marcia Belvin

机构：

[1] Genentech,Department of Translational Oncology

[2] Inc.,Department of Biochemical and Cellular Pharmacology

[3] 1 DNA Way,Department of Discovery Chemistry

[4] South San Francisco,Department of Discovery Oncology

[5] California 94080,Department of Structural Biology

[6] USA,undefined

[7] Genentech,undefined

[8] Inc.,undefined

[9] 1 DNA Way,undefined

[10] South San Francisco,undefined

[11] California 94080,undefined

[12] USA,undefined

[13] Genentech,undefined

[14] Inc.,undefined

[15] 1 DNA Way,undefined

[16] South San Francisco,undefined

[17] California 94080,undefined

[18] USA,undefined

[19] Argenta,undefined

[20] 8/9 Spire Green Centre,undefined

[21] Flex Meadow,undefined

[22] Harlow,undefined

[23] Essex CM19 5TR,undefined

[24] UK,undefined

[25] Genentech,undefined

[26] Inc.,undefined

[27] 1 DNA Way,undefined

[28] South San Francisco,undefined

[29] California 94080,undefined

[30] USA,undefined

[31] Genentech,undefined

[32] Inc.,undefined

[33] 1 DNA Way,undefined

[34] South San Francisco,undefined

[35] California 94080,undefined

[36] USA,undefined

[37] Present addresses: WestCHEM,undefined

[38] School of Chemistry,undefined

[39] University of Glasgow,undefined

[40] Joseph Black Building,undefined

[41] University Avenue,undefined

[42] Glasgow G12 8QQ,undefined

[43] UK (J.F.M.H.); MRC Mitochondrial Biology Unit,undefined

[44] Wellcome Trust/MRC Building,undefined

[45] Hills Road,undefined

[46] Cambridge CB2 OXY,undefined

[47] UK (A.P.); Novartis Institutes for Biomedical Research,undefined

[48] Fabrikstrasse 16,undefined

[49] CH-4002 Basel,undefined

[50] Switzerland (C.W.); Cairn Biosciences Inc.,undefined

来源：

Nature | 2013年 / 501卷

关键词：

D O I：

暂无

中图分类号：

学科分类号：

摘要：

The mechanism of action of three different allosteric MEK inhibitors that target the MAP kinase pathway is investigated, and their efficacy is shown to be explained by the distinct mechanisms regulating MEK activation in KRAS- versus BRAF-driven tumours; this work provides a rationale for designing more effective cancer therapies for these common genetic subtypes of cancer.

引用

页码：232 / 236

页数：4

共 40 条

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[23] Synergy of WEE1 and mTOR Inhibition in Mutant KRAS-Driven Lung Cancers
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[24] Dual inhibition of SUMOylation and MEK conquers MYC-expressing KRAS-mutant cancers by accumulating DNA damage
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[26] Doublet BRAF/MEK inhibition versus single-agent BRAF inhibition in the management of BRAF-mutant advanced melanoma, biological rationale and meta-analysis of published data
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[27] Doublet BRAF/MEK inhibition versus single-agent BRAF inhibition in the management of BRAF-mutant advanced melanoma, biological rationale and meta-analysis of published data
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[28] Comprehensive antitumor immune response boosted by dual inhibition of SUMOylation and MEK in MYC-expressing KRAS-mutant cancers
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[29] Low-Dose Vertical Inhibition of the RAF-MEK-ERK Cascade Causes Apoptotic Death of KRAS Mutant Cancers
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CELL REPORTS, 2020, 31 (11):
[30] BRAF Inhibitor-Driven Tumor Proliferation in a KRAS-Mutated Colon Carcinoma Is Not Overcome by MEK1/2 Inhibition
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JOURNAL OF CLINICAL ONCOLOGY, 2013, 31 (35) : E448 - E451

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