Systematic identification of genomic markers of drug sensitivity in cancer cells.
Systematic identification of genomic markers of drug sensitivity in cancer cells.
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DOI：
10.1038/nature11005
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发表时间：
2012-03-28
期刊：
影响因子：
64.8
通讯作者：
Benes, Cyril H.
中科院分区：
文献类型：
--
作者：
Garnett, Mathew J.;Edelman, Elena J.;Heidorn, Sonja J.;Greenman, Chris D.;Dastur, Anahita;Lau, King Wai;Greninger, Patricia;Thompson, I. Richard;Luo, Xi;Soares, Jorge;Liu, Qingsong;Iorio, Francesco;Surdez, Didier;Chen, Li;Milano, Randy J.;Bignell, Graham R.;Tam, Ah T.;Davies, Helen;Stevenson, Jesse A.;Barthorpe, Syd;Lutz, Stephen R.;Kogera, Fiona;Lawrence, Karl;McLaren-Douglas, Anne;Mitropoulos, Xeni;Mironenko, Tatiana;Thi, Helen;Richardson, Laura;Zhou, Wenjun;Jewitt, Frances;Zhang, Tinghu;O'Brien, Patrick;Boisvert, Jessica L.;Price, Stacey;Hur, Wooyoung;Yang, Wanjuan;Deng, Xianming;Butler, Adam;Choi, Hwan Geun;Chang, JaeWon;Baselga, Jose;Stamenkovic, Ivan;Engelman, Jeffrey A.;Sharma, Sreenath V.;Delattre, Olivier;Saez-Rodriguez, Julio;Gray, Nathanael S.;Settleman, Jeffrey;Futreal, P. Andrew;Haber, Daniel A.;Stratton, Michael R.;Ramaswamy, Sridhar;McDermott, Ultan;Benes, Cyril H.
临床对抗癌治疗的反应通常局限于一小部分患者。在某些情况下，突变的癌症基因是对靶向药物反应的有效生物标志物。为了发现对癌症治疗药物敏感和耐药的新生物标记物，我们筛选了一个由数百个癌细胞株组成的小组，这些细胞株代表了人类癌症的大部分组织类型和遗传多样性，130种药物正在进行临床和临床前研究。总而言之，我们发现突变的癌症基因与细胞对大多数目前可用的抗癌药物的反应有关。经典的癌基因成瘾模式被额外的组织特异性或表达生物标记物改变，一些频繁突变的基因与广泛的治疗药物的敏感性有关。发现了意想不到的关系，包括携带EWS-FLI1基因易位的尤文氏肉瘤细胞对PARP抑制剂的显著敏感性。通过将药物活性与癌症基因组的功能复杂性联系起来，癌症细胞系中的系统药物基因组学图谱为指导合理的癌症治疗策略提供了一个强大的生物标志物发现平台。
Clinical responses to anticancer therapies are often restricted to a subset of patients. In some cases, mutated cancer genes are potent biomarkers of response to targeted agents. To uncover new biomarkers of sensitivity and resistance to cancer therapeutics, we screened a panel of several hundred cancer cell lines, which represent much of the tissue-type and genetic diversity of human cancers, with 130 drugs under clinical and preclinical investigation. In aggregate, we found mutated cancer genes were associated with cellular response to most currently available cancer drugs. Classic oncogene addiction paradigms were modified by additional tissue-specific or expression biomarkers, and some frequently mutated genes were associated with sensitivity to a broad range of therapeutic agents. Unexpected relationships were revealed, including the marked sensitivity of Ewing’s sarcoma cells harboring the EWS-FLI1 gene translocation to PARP inhibitors. By linking drug activity to the functional complexity of cancer genomes, systematic pharmacogenomic profiling in cancer cell lines provides a powerful biomarker discovery platform to guide rational cancer therapeutic strategies.
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影响因子：
158.5
作者：
Lynch, TJ;Bell, DW;Haber, DA
通讯作者：
Haber, DA
影响因子：
158.5
作者：
Druker, Brian J.;Guilhot, Francois;Larson, Richard A.
通讯作者：
Larson, Richard A.
DOI：
10.1093/jnci/91.22.1940
发表时间：
1999-11-17
期刊：
JOURNAL OF THE NATIONAL CANCER INSTITUTE
影响因子：
--
作者：
Kelland, LR;Sharp, SY;Workman, P
通讯作者：
Workman, P
影响因子：
21.3
作者：
Hanafusa, H;Torii, S;Nishida, E
通讯作者：
Nishida, E
PICNIC：一种利用微阵列癌症数据预测绝对等位基因拷贝数变异的算法。
影响因子：
2.1
作者：
Greenman, Chris D.;Bignell, Graham;Butler, Adam;Edkins, Sarah;Hinton, Jon;Beare, Dave;Swamy, Sajani;Santarius, Thomas;Chen, Lina;Widaa, Sara;Futreal, P. Andy;Stratton, Michael R.
通讯作者：
Stratton, Michael R.