Chemistry-First Approach for Nomination of Personalized Treatment in Lung Cancer

被引：104

作者：

McMillan, Elizabeth A. ^{[1
]}

Ryu, Myung-Jeom ^{[2
]}

Diep, Caroline H. ^{[1
]}

Mendiratta, Saurabh ^{[1
]}

Clemenceau, Jean R. ^{[1
]}

Vaden, Rachel M. ^{[1
]}

Kim, Ju-Hwa ^{[2
]}

Motoyaji, Takashi ^{[3
]}

Covington, Kyle R. ^{[4
]}

Peyton, Michael ^{[5
]}

Huffman, Kenneth ^{[5
]}

Wu, Xiaofeng ^{[1
]}

Girard, Luc ^{[5
]}

Sung, Yeojin ^{[2
]}

Chen, Pei-Hsaun ^{[6
]}

Mallipeddi, Prema L. ^{[7
]}

Lee, Joo Young ^{[2
]}

Hanson, Jordan ^{[7
]}

Voruganti, Sukesh ^{[7
]}

Yu, Yunku ^{[8
]}

Park, Sunho ^{[8
]}

Sudderth, Jessica ^{[6
]}

DeSevo, Christopher ^{[1
]}

Muzny, Donna M. ^{[4
]}

Doddapaneni, HarshaVardhan ^{[4
]}

Gazdar, Adi ^{[12
]}

Gibbs, Richard A. ^{[4
]}

Hwang, Tae-Hyun ^{[8
]}

Heymach, John V. ^{[9
]}

Wistuba, Ignacio ^{[10
]}

Coombes, Kevin R. ^{[11
]}

Williams, Noelle S. ^{[7
]}

Wheeler, David A. ^{[4
]}

MacMillan, John B. ^{[7
]}

Deberardinis, Ralph J. ^{[6
]}

Roth, Michael G. ^{[7
]}

Posner, Bruce A. ^{[7
]}

Minna, John D. ^{[5
]}

Kim, Hyun Seok ^{[2
]}

White, Michael A. ^{[1
]}

机构：

[1] Univ Texas Southwestern Med Ctr Dallas, Dept Cell Biol, Dallas, TX 75390 USA

[2] Yonsei Univ, Coll Med, Brain Korea PLUS Project Med Sci 21, Severance Biomed Sci Inst, Seoul, South Korea

[3] Takeda Pharmaceut Co Ltd, Pharmaceut Res Div, Biomol Res Labs, Fujisawa, Kanagawa, Japan

[4] Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA

[5] Univ Texas Southwestern Med Ctr Dallas, Hamon Ctr Therapeut Oncol, Dallas, TX 75390 USA

[6] Univ Texas Southwestern Med Ctr Dallas, Childrens Res Inst, Dallas, TX 75390 USA

[7] Univ Texas Southwestern Med Ctr Dallas, Dept Biochem, Dallas, TX 75390 USA

[8] Univ Texas Southwestern Med Ctr Dallas, Dept Clin Sci, Dallas, TX 75390 USA

[9] Univ Texas MD Anderson Canc Ctr, Dept Thoracic Head & Neck Med Oncol, Houston, TX 77030 USA

[10] Univ Texas MD Anderson Canc Ctr, Translat Mol Pathol, Houston, TX 77030 USA

[11] Ohio State Univ, Dept Biomed Informat, Columbus, OH 43210 USA

[12] Univ Texas Southwestern Med Ctr Dallas, Dept Pathol, Dallas, TX 75390 USA

来源：

CELL | 2018年 / 173卷 / 04期

关键词：

SYSTEMATIC IDENTIFICATION; DRUG-SENSITIVITY; CELL-SURVIVAL; GLUT8; CONTRIBUTES; MECHANISM; TRANSPORT;

D O I：

10.1016/j.cell.2018.03.028

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Diversity in the genetic lesions that cause cancer is extreme. In consequence, a pressing challenge is the development of drugs that target patient-specific disease mechanisms. To address this challenge, we employed a chemistry-first discovery paradigm for de novo identification of druggable targets linked to robust patient selection hypotheses. In particular, a 200,000 compound diversity-oriented chemical library was profiled across a heavily annotated test-bed of >100 cellular models representative of the diverse and characteristic somatic lesions for lung cancer. This approach led to the delineation of 171 chemical-genetic associations, shedding light on the targetability of mechanistic vulnerabilities corresponding to a range of oncogenotypes present in patient populations lacking effective therapy. Chemically addressable addictions to ciliogenesis in TTC21B mutants and GLUT8-dependent serine biosynthesis in KRAS/KEAP1 double mutants are prominent examples. These observations indicate a wealth of actionable opportunities within the complex molecular etiology of cancer.

引用

页码：864 / +

页数：44

共 36 条

[1] 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

[2] Opposing role of Notch1 and Notch2 in a KrasG12D-driven murine non-small cell lung cancer model [J].

Baumgart, A. ;

Mazur, P. K. ;

Anton, M. ;

Rudelius, M. ;

Schwamborn, K. ;

Feuchtinger, A. ;

Behnke, K. ;

Walch, A. ;

Braren, R. ;

Peschel, C. ;

Duyster, J. ;

Siveke, J. T. ;

Dechow, T. .

ONCOGENE, 2015, 34 (05) :578-588

[3] GLUT8 is a glucose transporter responsible for insulin-stimulated glucose uptake in the blastocyst [J].

Carayannopoulos, MO ;

Chi, MMY ;

Cui, Y ;

Pingsterhaus, JM ;

McKnight, RA ;

Mueckler, M ;

Devaskar, SU ;

Moley, KH .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2000, 97 (13) :7313-7318

[4] Identification of novel NRF2-regulated genes by ChIP-Seq: influence on retinoid X receptor alpha [J].

Chorley, Brian N. ;

Campbell, Michelle R. ;

Wang, Xuting ;

Karaca, Mehmet ;

Sambandan, Deepa ;

Bangura, Fatu ;

Xue, Peng ;

Pi, Jingbo ;

Kleeberger, Steven R. ;

Bell, Douglas A. .

NUCLEIC ACIDS RESEARCH, 2012, 40 (15) :7416-7429

[5]

Chu D, 2011, ANN ONCOL, V22, P2440, DOI 10.1093/annonc/mdq776

[6] TTC21B contributes both causal and modifying alleles across the ciliopathy spectrum [J].

Davis, Erica E. ;

Zhang, Qi ;

Liu, Qin ;

Diplas, Bill H. ;

Davey, Lisa M. ;

Hartley, Jane ;

Stoetzel, Corinne ;

Szymanska, Katarzyna ;

Ramaswami, Gokul ;

Logan, Clare V. ;

Muzny, Donna M. ;

Young, Alice C. ;

Wheeler, David A. ;

Cruz, Pedro ;

Morgan, Margaret ;

Lewis, Lora R. ;

Cherukuri, Praveen ;

Maskeri, Baishali ;

Hansen, Nancy F. ;

Mullikin, James C. ;

Blakesley, Robert W. ;

Bouffard, Gerard G. ;

Gyapay, Gabor ;

Rieger, Susanne ;

Toenshoff, Burkhard ;

Kern, Ilse ;

Soliman, Neveen A. ;

Neuhaus, Thomas J. ;

Swoboda, Kathryn J. ;

Kayserili, Hulya ;

Gallagher, Tomas E. ;

Lewis, Richard A. ;

Bergmann, Carsten ;

Otto, Edgar A. ;

Saunier, Sophie ;

Scambler, Peter J. ;

Beales, Philip L. ;

Gleeson, Joseph G. ;

Maher, Eamonn R. ;

Attie-Bitach, Tania ;

Dollfus, Helene ;

Johnson, Colin A. ;

Green, Eric D. ;

Gibbs, Richard A. ;

Hildebrandt, Friedhelm ;

Pierce, Eric A. ;

Katsanis, Nicholas .

NATURE GENETICS, 2011, 43 (03) :189-U28

[7] Molecular basis of ligand recognition and transport by glucose transporters [J].

Deng, Dong ;

Sun, Pengcheng ;

Yan, Chuangye ;

Ke, Meng ;

Jiang, Xin ;

Xiong, Lei ;

Ren, Wenlin ;

Hirata, Kunio ;

Yamamoto, Masaki ;

Fan, Shilong ;

Yan, Nieng .

NATURE, 2015, 526 (7573) :391-+

[8] STAR: ultrafast universal RNA-seq aligner [J].

Dobin, Alexander ;

Davis, Carrie A. ;

Schlesinger, Felix ;

Drenkow, Jorg ;

Zaleski, Chris ;

Jha, Sonali ;

Batut, Philippe ;

Chaisson, Mark ;

Gingeras, Thomas R. .

BIOINFORMATICS, 2013, 29 (01) :15-21

[9] Biomarker Accessible and Chemically Addressable Mechanistic Subtypes of BRAF Melanoma [J].

Eskiocak, Banu ;

McMillan, Elizabeth A. ;

Mendiratta, Saurabh ;

Kollipara, Rahul K. ;

Zhang, Hailei ;

Humphries, Caroline G. ;

Wang, Changguang ;

Garcia-Rodriguez, Jose ;

Ding, Ming ;

Zaman, Aubhishek ;

Rosales, Tracy I. ;

Eskiocak, Ugur ;

Smith, Michael P. ;

Sudderth, Jessica ;

Komurov, Kakajan ;

Deberardinis, Ralph J. ;

Wellbrock, Claudia ;

Davies, Michael A. ;

Wargo, Jennifer A. ;

Yu, Yonghao ;

De Brabander, Jef K. ;

Williams, Noelle S. ;

Chin, Lynda ;

Rizos, Helen ;

Long, Georgina V. ;

Kittler, Ralf ;

White, Michael A. .

CANCER DISCOVERY, 2017, 7 (08) :832-851

[10] Clustering by passing messages between data points [J].

Frey, Brendan J. ;

Dueck, Delbert .

SCIENCE, 2007, 315 (5814) :972-976

← 1 2 3 4 →