Network dynamics-based cancer panel stratification for systemic prediction of anticancer drug response.
Network dynamics-based cancer panel stratification for systemic prediction of anticancer drug response.
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DOI：
10.1038/s41467-017-02160-5
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发表时间：
2017-12-05
影响因子：
16.6
通讯作者：
Cho KH
中科院分区：
文献类型：
--
作者：
Choi M;Shi J;Zhu Y;Yang R;Cho KH
Cancer is a complex disease involving multiple genomic alterations that disrupt the dynamic response of signaling networks. The heterogeneous nature of cancer, which results in highly variable drug response, is a major obstacle to developing effective cancer therapy. Previous studies of cancer therapeutic response mostly focus on static analysis of genome-wide alterations, thus they are unable to unravel the dynamic, network-specific origin of variation. Here we present a network dynamics-based approach to integrate cancer genomics with dynamics of biological network for drug response prediction and design of drug combination. We select the p53 network as an example and analyze its cancer-specific state transition dynamics under distinct anticancer drug treatments by attractor landscape analysis. Our results not only enable stratification of cancer into distinct drug response groups, but also reveal network-specific drug targets that maximize p53 network-mediated cell death, providing a basis to design combinatorial therapeutic strategies for distinct cancer genomic subtypes. Genomic alterations underlie the variability of drug responses between cancers, but our mechanistic understanding is limited. Here the authors use the p53 network to study how rewiring of signalling networks by genomic alterations impact their dynamic response to pharmacological perturbation.
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DOI：
10.1126/science.1226344
发表时间：
2012-10-12
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Iyer G;Hanrahan AJ;Milowsky MI;Al-Ahmadie H;Scott SN;Janakiraman M;Pirun M;Sander C;Socci ND;Ostrovnaya I;Viale A;Heguy A;Peng L;Chan TA;Bochner B;Bajorin DF;Berger MF;Taylor BS;Solit DB
通讯作者：
Solit DB
影响因子：
7.3
作者：
Gao J;Aksoy BA;Dogrusoz U;Dresdner G;Gross B;Sumer SO;Sun Y;Jacobsen A;Sinha R;Larsson E;Cerami E;Sander C;Schultz N
通讯作者：
Schultz N
影响因子：
3.7
作者：
Abou-Jaoudé W;Traynard P;Monteiro PT;Saez-Rodriguez J;Helikar T;Thieffry D;Chaouiya C
通讯作者：
Chaouiya C
影响因子：
16.6
作者：
Domcke, Silvia;Sinha, Rileen;Levine, Douglas A.;Sander, Chris;Schultz, Nikolaus
通讯作者：
Schultz, Nikolaus
影响因子：
64.8
作者：
通讯作者：
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