The NCI Transcriptional Pharmacodynamics Workbench: A Tool to Examine Dynamic Expression Profiling of Therapeutic Response in the NCI-60 Cell Line Panel.
Anne Monks,Yingdong Zhao,Curtis Hose,Hossein A. Hamed,Julia Krushkal,Jianwen Fang,Dmitriy Sonkin,Alida Palmisano,Eric C. Polley,Laura K. Fogli,Mariam M. Konaté,Sarah B. Miller,Melanie A. Simpson,Andrea Regier Voth,Ming Chung Li,Erik Harris,Xiaolin Wu,John Connelly,Annamaria Rapisarda,Beverly A. Teicher,Richard Simon,James H. Doroshow +21 more
TLDR
The NCI Transcriptional Pharmacodynamics Workbench represents the most extensive compilation to date of directly measured longitudinal transcriptional responses to anticancer agents across a thoroughly characterized ensemble of cancer cell lines.Abstract:
The intracellular effects and overall efficacies of anticancer therapies can vary significantly by tumor type. To identify patterns of drug-induced gene modulation that occur in different cancer cell types, we measured gene-expression changes across the NCI-60 cell line panel after exposure to 15 anticancer agents. The results were integrated into a combined database and set of interactive analysis tools, designated the NCI Transcriptional Pharmacodynamics Workbench (NCI TPW), that allows exploration of gene-expression modulation by molecular pathway, drug target, and association with drug sensitivity. We identified common transcriptional responses across agents and cell types and uncovered gene-expression changes associated with drug sensitivity. We also demonstrated the value of this tool for investigating clinically relevant molecular hypotheses and identifying candidate biomarkers of drug activity. The NCI TPW, publicly available at https://tpwb.nci.nih.gov, provides a comprehensive resource to facilitate understanding of tumor cell characteristics that define sensitivity to commonly used anticancer drugs. Significance: The NCI Transcriptional Pharmacodynamics Workbench represents the most extensive compilation to date of directly measured longitudinal transcriptional responses to anticancer agents across a thoroughly characterized ensemble of cancer cell lines.read more
Citations
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Quantitative Proteome Landscape of the NCI-60 Cancer Cell Lines.
Tiannan Guo,Tiannan Guo,Augustin Luna,Vinodh N. Rajapakse,Ching Chiek Koh,Zhicheng Wu,Wei Liu,Yaoting Sun,Huanhuan Gao,Michael P. Menden,Chao Xu,Laurence Calzone,Loredana Martignetti,Chiara Auwerx,Marija Buljan,Amir Banaei-Esfahani,Alessandro Ori,Murat Iskar,Ludovic C Gillet,Ran Bi,Jiangnan Zhang,Huanhuan Zhang,Chenhuan Yu,Qing Zhong,Sudhir Varma,Uwe Schmitt,Peng Qiu,Qiushi Zhang,Yi Zhu,Yi Zhu,Peter J. Wild,Mathew J. Garnett,Peer Bork,Martin Beck,Kexin Liu,Julio Saez-Rodriguez,Fathi Elloumi,William C. Reinhold,Chris Sander,Yves Pommier,Ruedi Aebersold,Ruedi Aebersold +41 more
TL;DR: A novel proteome resource for the NCI-60 cell lines generated by pressure cycling technology and SWATH mass spectrometry is presented, together with relevant software tools, and the value of proteome data in predicting drug response for over 240 clinically relevant chemotherapeutic and targeted therapies is demonstrated.
Posted ContentDOI
Connecting omics signatures of diseases, drugs, and mechanisms of actions with iLINCS
Marcin Pilarczyk,Michal Kouril,Behrouz Shamsaei,Juozas Vasiliauskas,Wen Niu,Naim Al Mahi,Lixia Zhang,Nicholas A. Clark,Yan Ren,Shana White,Rashid Saadman Karim,Huan Xu,Jacek Biesiada,Mark F. Bennett,Sarah E. Davidson,John F. Reichard,Kurt Roberts,Vasileios Stathias,Amar Koleti,Dusica Vidovic,Daniel J.B. Clarke,Stephan C. Schürer,Avi Ma'ayan,Jarek Meller,Jarek Meller,Mario Medvedovic +25 more
TL;DR: In summary, iLINCS workflows integrate vast omics data resources and a range of analytics and interactive visualization tools into a comprehensive platform for analysis of omics signatures.
Journal ArticleDOI
Chromatin Remodeling and Immediate Early Gene Activation by SLFN11 in Response to Replication Stress.
Junko Murai,Hongliang Zhang,Lorinc Pongor,Sai-Wen Tang,Ukhyun Jo,Fumiya Moribe,Yixiao Ma,Masaru Tomita,Yves Pommier +8 more
TL;DR: It is shown that SLFN11 increases chromatin accessibility genome wide, prominently at active promoters in response to replication stress induced by the checkpoint kinase 1 inhibitor prexasertib or the topoisomerase I (TOP1) inhibitor camptothecin.
Journal ArticleDOI
Sorafenib Inhibits Ribonucleotide Reductase Regulatory Subunit M2 (RRM2) in Hepatocellular Carcinoma Cells.
TL;DR: Mining the cancer genomics and proteomics data revealed that ribonucleotide reductase regulatory subunit M2 (RRM2) serves as a prognosis biomarker and a therapeutic target for HCC.
Journal ArticleDOI
mTOR/EGFR/iNOS/MAP2K1/FGFR/TGFB1 Are Druggable Candidates for N-(2,4-Difluorophenyl)-2′,4′-Difluoro-4-Hydroxybiphenyl-3-Carboxamide (NSC765598), With Consequent Anticancer Implications
Bashir Lawal,Bashir Lawal,Ching-Yu Lee,Ching-Yu Lee,Ntlotlang Mokgautsi,Ntlotlang Mokgautsi,Maryam Rachmawati Sumitra,Harshita Khedkar,Alexander T.H. Wu,Hsu Shan Huang +9 more
TL;DR: In this article, the ligand-protein interactions of NSC765598 with its potential targets and to evaluate its anticancer activities in vitro have been investigated and compared with NCI standard agents.
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Journal ArticleDOI
The Cancer Cell Line Encyclopedia enables predictive modelling of anticancer drug sensitivity
Jordi Barretina,Giordano Caponigro,Nicolas Stransky,Kavitha Venkatesan,Adam A. Margolin,Adam A. Margolin,Sungjoon Kim,Christine D. Wilson,Joseph Lehar,Gregory V. Kryukov,Dmitriy Sonkin,Anupama Reddy,Manway Liu,Lauren Murray,Michael F. Berger,Michael F. Berger,John Monahan,Paula Morais,Jodi Meltzer,Adam Korejwa,Judit Jané-Valbuena,Judit Jané-Valbuena,Felipa A. Mapa,Joseph Thibault,Eva Bric-Furlong,Pichai Raman,Aaron Shipway,Ingo H. Engels,Jill Cheng,Guoying K. Yu,Jianjun Yu,Peter Aspesi,Melanie de Silva,Kalpana Jagtap,Michael D. Jones,Li Wang,Charlie Hatton,Emanuele Palescandolo,Supriya Gupta,Scott Mahan,Carrie Sougnez,Robert C. Onofrio,Ted Liefeld,Laura E. MacConaill,Wendy Winckler,Michael R. Reich,Nanxin Li,Jill P. Mesirov,Stacey Gabriel,Gad Getz,Kristin G. Ardlie,Vivien W. Chan,Vic E. Myer,Barbara L. Weber,Jeffrey A. Porter,Markus Warmuth,Peter Finan,Jennifer L. Harris,Matthew Meyerson,Matthew Meyerson,Todd R. Golub,Michael Morrissey,William R. Sellers,Robert Schlegel,Levi A. Garraway,Levi A. Garraway +65 more
TL;DR: The results indicate that large, annotated cell-line collections may help to enable preclinical stratification schemata for anticancer agents and the generation of genetic predictions of drug response in the preclinical setting and their incorporation into cancer clinical trial design could speed the emergence of ‘personalized’ therapeutic regimens.
Journal ArticleDOI
The Connectivity Map: Using Gene-Expression Signatures to Connect Small Molecules, Genes, and Disease
Justin Lamb,Emily D. Crawford,David Peck,Joshua W. Modell,Irene C. Blat,Matthew J. Wrobel,Jim Lerner,Jean Philippe Brunet,Aravind Subramanian,Kenneth N. Ross,Michael Reich,Haley Hieronymus,Haley Hieronymus,Guo Wei,Guo Wei,Scott A. Armstrong,Scott A. Armstrong,Stephen J. Haggarty,Stephen J. Haggarty,Paul A. Clemons,Ru Wei,Steven A. Carr,Eric S. Lander,Eric S. Lander,Todd R. Golub +24 more
TL;DR: The first installment of a reference collection of gene-expression profiles from cultured human cells treated with bioactive small molecules is created, and it is demonstrated that this “Connectivity Map” resource can be used to find connections among small molecules sharing a mechanism of action, chemicals and physiological processes, and diseases and drugs.
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