Studying clonal dynamics in response to cancer therapy using high-complexity barcoding

被引：371

作者：

Bhang, Hyo-eun C. ^{[1
]}

Ruddy, David A. ^{[2
]}

Radhakrishna, Viveksagar Krishnamurthy ^{[1
]}

Caushi, Justina X. ^{[1
]}

Zhao, Rui ^{[3
,4
]}

Hims, Matthew M. ^{[1
]}

Singh, Angad P. ^{[1
]}

Kao, Iris ^{[2
]}

Rakiec, Daniel ^{[2
]}

Shaw, Pamela ^{[2
]}

Balak, Marissa ^{[2
]}

Raza, Alina ^{[1
]}

Ackley, Elizabeth ^{[2
]}

Keen, Nicholas ^{[1
]}

Schlabach, Michael R. ^{[1
]}

Palmer, Michael ^{[2
]}

Leary, Rebecca J. ^{[1
]}

Chiang, Derek Y. ^{[1
]}

Sellers, William R. ^{[1
]}

Michor, Franziska ^{[3
,4
]}

Cooke, Vesselina G. ^{[1
]}

Korn, Joshua M. ^{[1
]}

Stegmeier, Frank ^{[1
]}

机构：

[1] Novartis Inst Biomed Res, Oncol Dis Area, Cambridge, MA 02139 USA

[2] Novartis Inst Biomed Res, Translat Clin Oncol, Cambridge, MA USA

[3] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA

[4] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA

来源：

NATURE MEDICINE | 2015年 / 21卷 / 05期

关键词：

CHRONIC MYELOID-LEUKEMIA; ABL KINASE DOMAIN; BCR-ABL; ACQUIRED-RESISTANCE; LUNG-CANCER; MET AMPLIFICATION; EGFR INHIBITORS; DRUG-SENSITIVITY; RARE MUTATIONS; GENE-MUTATIONS;

D O I：

10.1038/nm.3841

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

070307 [化学生物学]; 071010 [生物化学与分子生物学];

摘要：

Resistance to cancer therapies presents a significant clinical challenge. Recent studies have revealed intratumoral heterogeneity as a source of therapeutic resistance. However, it is unclear whether resistance is driven predominantly by pre-existing or de novo alterations, in part because of the resolution limits of next-generation sequencing. To address this, we developed a high-complexity barcode library, ClonTracer, which enables the high-resolution tracking of more than 1 million cancer cells under drug treatment. In two clinically relevant models, ClonTracer studies showed that the majority of resistant clones were part of small, pre-existing subpopulations that selectively escaped under therapeutic challenge. Moreover, the ClonTracer approach enabled quantitative assessment of the ability of combination treatments to suppress resistant clones. These findings suggest that resistant clones are present before treatment, which would make up-front therapeutic combinations that target non-overlapping resistance a preferred approach. Thus, ClonTracer barcoding may be a valuable tool for optimizing therapeutic regimens with the goal of curative combination therapies for cancer.

引用

页码：440 / U207

页数：13

共 57 条

[1]

Allosteric inhibitors of Bcr-abl-dependent cell proliferation [J].

Adrián, FJ ;

Ding, Q ;

Sim, TB ;

Velentza, A ;

Sloan, C ;

Liu, Y ;

Zhang, GB ;

Hur, W ;

Ding, S ;

Manley, P ;

Mestan, J ;

Fabbro, D ;

Gray, NS .

NATURE CHEMICAL BIOLOGY, 2006, 2 (02) :95-102

[2]

Amann J, 2005, CANCER RES, V65, P226

[3]

The Cancer Cell Line Encyclopedia enables predictive modelling of anticancer drug sensitivity [J].

Barretina, Jordi ;

Caponigro, Giordano ;

Stransky, Nicolas ;

Venkatesan, Kavitha ;

Margolin, Adam A. ;

Kim, Sungjoon ;

Wilson, Christopher J. ;

Lehar, Joseph ;

Kryukov, Gregory V. ;

Sonkin, Dmitriy ;

Reddy, Anupama ;

Liu, Manway ;

Murray, Lauren ;

Berger, Michael F. ;

Monahan, John E. ;

Morais, Paula ;

Meltzer, Jodi ;

Korejwa, Adam ;

Jane-Valbuena, Judit ;

Mapa, Felipa A. ;

Thibault, Joseph ;

Bric-Furlong, Eva ;

Raman, Pichai ;

Shipway, Aaron ;

Engels, Ingo H. ;

Cheng, Jill ;

Yu, Guoying K. ;

Yu, Jianjun ;

Aspesi, Peter, Jr. ;

de Silva, Melanie ;

Jagtap, Kalpana ;

Jones, Michael D. ;

Wang, Li ;

Hatton, Charles ;

Palescandolo, Emanuele ;

Gupta, Supriya ;

Mahan, Scott ;

Sougnez, Carrie ;

Onofrio, Robert C. ;

Liefeld, Ted ;

MacConaill, Laura ;

Winckler, Wendy ;

Reich, Michael ;

Li, Nanxin ;

Mesirov, Jill P. ;

Gabriel, Stacey B. ;

Getz, Gad ;

Ardlie, Kristin ;

Chan, Vivien ;

Myer, Vic E. .

NATURE, 2012, 483 (7391) :603-607

[4]

MET amplification occurs with or without T790M mutations in EGFR mutant lung tumors with acquired resistance to gefitinib or erlotinib [J].

Bean, James ;

Brennan, Cameron ;

Shih, Jin-Yuan ;

Riely, Gregory ;

Viale, Agnes ;

Wang, Lu ;

Chitale, Dhananjay ;

Motoi, Noriko ;

Szoke, Janos ;

Broderick, Stephen ;

Balak, Marissa ;

Chang, Wen-Cheng ;

Yu, Chong-Jen ;

Gazdar, Adi ;

Pass, Harvey ;

Rusch, Valerie ;

Gerald, William ;

Huang, Shiu-Feng ;

Yang, Pan-Chyr ;

Miller, Vincent ;

Ladany, Marc ;

Yang, Chih-Hsin ;

Pao, William .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2007, 104 (52) :20932-20937

[5]

Evolutionary dynamics of cancer in response to targeted combination therapy [J].

Bozic, Ivana ;

Reiter, Johannes G. ;

Allen, Benjamin ;

Antal, Tibor ;

Chatterjee, Krishnendu ;

Shah, Preya ;

Moon, Yo Sup ;

Yaqubie, Amin ;

Kelly, Nicole ;

Le, Dung T. ;

Lipson, Evan J. ;

Chapman, Paul B. ;

Diaz, Luis A., Jr. ;

Vogelstein, Bert ;

Nowak, Martin A. .

ELIFE, 2013, 2

[6]

An Epithelial-Mesenchymal Transition Gene Signature Predicts Resistance to EGFR and PI3K Inhibitors and Identifies Axl as a Therapeutic Target for Overcoming EGFR Inhibitor Resistance [J].

Byers, Lauren Averett ;

Diao, Lixia ;

Wang, Jing ;

Saintigny, Pierre ;

Girard, Luc ;

Peyton, Michael ;

Shen, Li ;

Fan, Youhong ;

Giri, Uma ;

Tumula, Praveen K. ;

Nilsson, Monique B. ;

Gudikote, Jayanthi ;

Tran, Hai ;

Cardnell, Robert J. G. ;

Bearss, David J. ;

Warner, Steven L. ;

Foulks, Jason M. ;

Kanner, Steven B. ;

Gandhi, Varsha ;

Krett, Nancy ;

Rosen, Steven T. ;

Kim, Edward S. ;

Herbst, Roy S. ;

Blumenschein, George R. ;

Lee, J. Jack ;

Lippman, Scott M. ;

Ang, K. Kian ;

Mills, Gordon B. ;

Hong, Waun K. ;

Weinstein, John N. ;

Wistuba, Ignacio I. ;

Coombes, Kevin R. ;

Minna, John D. ;

Heymach, John V. .

CLINICAL CANCER RESEARCH, 2013, 19 (01) :279-290

[7]

The cBio Cancer Genomics Portal: An Open Platform for Exploring Multidimensional Cancer Genomics Data [J].

Cerami, Ethan ;

Gao, Jianjiong ;

Dogrusoz, Ugur ;

Gross, Benjamin E. ;

Sumer, Selcuk Onur ;

Aksoy, Buelent Arman ;

Jacobsen, Anders ;

Byrne, Caitlin J. ;

Heuer, Michael L. ;

Larsson, Erik ;

Antipin, Yevgeniy ;

Reva, Boris ;

Goldberg, Arthur P. ;

Sander, Chris ;

Schultz, Nikolaus .

CANCER DISCOVERY, 2012, 2 (05) :401-404

[8]

Serum Concentrations of Erlotinib at a Dose of 25 mg Daily [J].

Costa, Daniel B. ;

Kobayashi, Susumu ;

Yeo, Wee-Lee ;

Hamada, Akinobu .

JOURNAL OF THORACIC ONCOLOGY, 2010, 5 (08) :1311-1312

[9]

A framework for variation discovery and genotyping using next-generation DNA sequencing data [J].

DePristo, Mark A. ;

Banks, Eric ;

Poplin, Ryan ;

Garimella, Kiran V. ;

Maguire, Jared R. ;

Hartl, Christopher ;

Philippakis, Anthony A. ;

del Angel, Guillermo ;

Rivas, Manuel A. ;

Hanna, Matt ;

McKenna, Aaron ;

Fennell, Tim J. ;

Kernytsky, Andrew M. ;

Sivachenko, Andrey Y. ;

Cibulskis, Kristian ;

Gabriel, Stacey B. ;

Altshuler, David ;

Daly, Mark J. .

NATURE GENETICS, 2011, 43 (05) :491-+

[10]

The molecular evolution of acquired resistance to targeted EGFR blockade in colorectal cancers [J].

Diaz, Luis A., Jr. ;

Williams, Richard T. ;

Wu, Jian ;

Kinde, Isaac ;

Hecht, J. Randolph ;

Berlin, Jordan ;

Allen, Benjamin ;

Bozic, Ivana ;

Reiter, Johannes G. ;

Nowak, Martin A. ;

Kinzler, Kenneth W. ;

Oliner, Kelly S. ;

Vogelstein, Bert .

NATURE, 2012, 486 (7404) :537-540

← 1 2 3 4 5 6 →