Cited by 714Cancer Mechanisms and TherapyProtein Kinase Regulation and GTPase SignalingComputational Drug Discovery Methods

The DOI matches its Crossref record; 100 of the 104 references it cites were found in a registry or an index.

Targeting the cancer kinome through polypharmacology

Open access

Knight, Zachary A., Lin, Henry, Shokat, Kevan M.·2010·Nature reviews. Cancer

DOI 10.1038/nrc2787PMC PMC2880454

Open this paper in CoChat — free account

Abstract

Kinase inhibitors are the largest class of new cancer drugs. However, it is already apparent that most tumours can escape from the inhibition of any single kinase. If it is necessary to inhibit multiple kinases, how do we choose which ones? In this Opinion article, we discuss some of the strategies that are currently being used to identify new therapeutic combinations of kinase targets.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

Integrity signals

Registry

Crossref · 10.1038/nrc2787

Cites

100 of 100 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Mutations of the BRAF gene in human cancer
Davies, H., Bignell, G. R., Cox, C., Stephens, P., Edkins, S., Clegg, S., Teague, J., Woffendin, H., Garnett, M. J., Bottomley, W., et al. (2002) · Nature · doi:10.1038/nature00766 · Cited by 10,674
The protein kinase complement of the human genome
Manning, G., Whyte, D. B., Martinez, R., Hunter, T., & Sudarsanam, S. (2002) · Science · doi:10.1126/science.1075762 · Cited by 8,145
Paclitaxel–Carboplatin Alone or with Bevacizumab for Non–Small-Cell Lung Cancer
Sandler, A., Gray, R., Perry, M. C., Brahmer, J., Schiller, J. H., Dowlati, A., Lilenbaum, R., & Johnson, D. H. (2006) · New England Journal of Medicine · doi:10.1056/nejmoa061884 · Cited by 5,761
Sunitinib versus Interferon Alfa in Metastatic Renal-Cell Carcinoma
Motzer, R. J., Hutson, T. E., Tomczak, P., Michaelson, M. D., Bukowski, R. M., Rixe, O., Oudard, S. M., Négrier, S., Szczylik, C. A., Kim, S. T., et al. (2007) · New England Journal of Medicine · doi:10.1056/nejmoa065044 · Cited by 5,752
Erlotinib in Previously Treated Non–Small-Cell Lung Cancer
Shepherd, F. A., Rodrigues Pereira, J., Ciuleanu, T., Tan, E. H., Hirsh, V., Thongprasert, S., Campos, D., Maoleekoonpiroj, S., Smylie, M., Martins, R., et al. (2005) · New England Journal of Medicine · doi:10.1056/nejmoa050753 · Cited by 5,419
Efficacy and Safety of a Specific Inhibitor of the BCR-ABL Tyrosine Kinase in Chronic Myeloid Leukemia
Druker, B. J., Talpaz, M., Resta, D. J., Peng, B., Buchdunger, E., Ford, J., Lydon, N., Kantarjian, H. M., Capdeville, R., Ohno-Jones, S., et al. (2001) · New England Journal of Medicine · doi:10.1056/nejm200104053441401 · Cited by 5,237
Sorafenib in Advanced Clear-Cell Renal-Cell Carcinoma
Escudier, B. J., Eisen, T. G., Stadler, W. M., Szczylik, C. A., Oudard, S. M., Siebels, M., Négrier, S., Chevreau, C., Solska, E., Desai, A. A., et al. (2007) · New England Journal of Medicine · doi:10.1056/nejmoa060655 · Cited by 4,802
Network pharmacology: the next paradigm in drug discovery
Hopkins, A. L. (2008) · Nature Chemical Biology · doi:10.1038/nchembio.118 · Cited by 4,622
MET Amplification Leads to Gefitinib Resistance in Lung Cancer by Activating ERBB3 Signaling
Engelman, J. A., Zejnullahu, K., Mitsudomi, T., Song, Y., Hyland, C., Park, J. O., Lindeman, N., Gale, C.-M., Zhao, X., Christensen, J., et al. (2007) · Science · doi:10.1126/science.1141478 · Cited by 4,496
Specificity and mechanism of action of some commonly used protein kinase inhibitors
DAVIES, S. P., Reddy, H., Caivano, M., & Cohen, P. (2000) · Biochemical Journal · doi:10.1042/0264-6021:3510095 · Cited by 4,366
Systematic RNA interference reveals that oncogenic KRAS-driven cancers require TBK1
Barbie, D. A., Tamayo, P., Boehm, J. S., Kim, S. Y., Moody, S. E., Dunn, I. F., Schinzel, A. C., Sandy, P., Meylan, E., Scholl, C., et al. (2009) · Nature · doi:10.1038/nature08460 · Cited by 3,922
Erlotinib plus gemcitabine compared with gemcitabine alone in patients with advanced pancreatic cancer: a phase III trial of the National Cancer Institute of Canada Clinical Trials Group
Moore, M. J., Goldstein, D., Hamm, J., Figer, A., Hecht, J. R., Gallinger, S., Au, H. J., Murawa, P., Walde, D., Wolff, R. A., et al. (2007) · Journal of Clinical Oncology · doi:10.1200/jco.2006.07.9525 · Cited by 3,848
K-ras Mutations and Benefit from Cetuximab in Advanced Colorectal Cancer
Karapetis, C. S., Khambata-Ford, S., Jonker, D. J., O'Callaghan, C. J., Tu, D., Tebbutt, N. C., Simes, R. J., Chalchal, H., Shapiro, J. D., Robitaille, S., et al. (2008) · New England Journal of Medicine · doi:10.1056/nejmoa0804385 · Cited by 3,622
Acquired Resistance of Lung Adenocarcinomas to Gefitinib or Erlotinib Is Associated with a Second Mutation in the EGFR Kinase Domain
Pao, W., Miller, V. A., Politi, K. A., Riely, G. J., Somwar, R., Zakowski, M. F., Kris, M. G., & Varmus, H. (2005) · PLoS Medicine · doi:10.1371/journal.pmed.0020073 · Cited by 3,527
Five-Year Follow-up of Patients Receiving Imatinib for Chronic Myeloid Leukemia
Druker, B. J., Guilhot, F., O’Brien, S. G., Gathmann, I., Kantarjian, H. M., Gattermann, N., Deininger, M. W., Silver, R. T., Goldman, J. M., Stone, R. M., et al. (2006) · New England Journal of Medicine · doi:10.1056/nejmoa062867 · Cited by 3,516
Lapatinib plus Capecitabine for HER2-Positive Advanced Breast Cancer
Geyer, C. E., Forster, J. K., Lindquist, D. L., Chan, S. Y. T., Romieu, C. G., Pieńkowski, T., Jagiełło-Gruszfeld, A., Crown, J. P., Chan, A., Kaufman, B., et al. (2006) · New England Journal of Medicine · doi:10.1056/nejmoa064320 · Cited by 3,458
Anorexigenic and Orexigenic Hormone Modulation of Mammalian Target of Rapamycin Complex 1 Activity and the Regulation of Hypothalamic Agouti-Related Protein mRNA Expression
Watterson, K. R., Bestow, D., Gallagher, J. R., Hamilton, D. L., Ashford, F. B., Meakin, P. J., & Ashford, M. L. J. (2012) · Neurosignals · doi:10.1159/000334144 · Cited by 3,395
The Consensus Coding Sequences of Human Breast and Colorectal Cancers
Sjöblom, T., Jones, S., Wood, L. D., Parsons, D. W., Lin, J., Barber, T. D., Mandelker, D. L., Leary, R. J., Ptak, J., Silliman, N., et al. (2006) · Science · doi:10.1126/science.1133427 · Cited by 3,161
Clinical Resistance to STI-571 Cancer Therapy Caused by BCR-ABL Gene Mutation or Amplification
Gorre, M. E., Mohammed, M., Ellwood, K., Hsu, N., Paquette, R., Rao, P. N., & Sawyers, C. L. (2001) · Science · doi:10.1126/science.1062538 · Cited by 3,104
Paclitaxel plus Bevacizumab versus Paclitaxel Alone for Metastatic Breast Cancer
Miller, K. D., Wang, M., Gralow, J. R., Dickler, M. N., Cobleigh, M., Perez, E. A., Shenkier, T. N., Cella, D. F., & Davidson, N. E. (2007) · New England Journal of Medicine · doi:10.1056/nejmoa072113 · Cited by 3,104
Efficacy of everolimus in advanced renal cell carcinoma: a double-blind, randomised, placebo-controlled phase III trial
Motzer, R. J., Escudier, B., Oudard, S., Hutson, T. E., Porta, C., Bracarda, S., Grünwald, V., Thompson, J. A., Figlin, R. A., Hollaender, N., et al. (2008) · The Lancet · doi:10.1016/s0140-6736(08)61039-9 · Cited by 3,019
The Genomic Landscapes of Human Breast and Colorectal Cancers
Wood, L. D., Parsons, D. W., Jones, S., Lin, J., Sjöblom, T., Leary, R. J., Shen, D., Boca, S. M., Barber, T., Ptak, J., et al. (2007) · Science · doi:10.1126/science.1145720 · Cited by 2,833
A Randomized Trial of Bevacizumab, an Anti–Vascular Endothelial Growth Factor Antibody, for Metastatic Renal Cancer
Yang, J. C., Haworth, L. R., Sherry, R. M., Hwu, P., Schwartzentruber, D. J., Topalian, S. L., Steinberg, S. M., Chen, H. X., & Rosenberg, S. A. (2003) · New England Journal of Medicine · doi:10.1056/nejmoa021491 · Cited by 2,704
Trastuzumab — Mechanism of Action and Use in Clinical Practice
Hudis, C. A. (2007) · New England Journal of Medicine · doi:10.1056/nejmra043186 · Cited by 2,640
The selectivity of protein kinase inhibitors: a further update
Bain, J., Plater, L., Elliott, M., Shpiro, N., Hastie, C. J., McLauchlan, H., Klevernic, I. V., Arthur, J. S. C., Alessi, D. R., & Cohen, P. (2007) · Biochemical Journal · doi:10.1042/bj20070797 · Cited by 2,522
A quantitative analysis of kinase inhibitor selectivity
Karaman, M. W., Herrgard, S., Treiber, D. K., Gallant, P., Atteridge, C. E., Campbell, B. T., Chan, K. W., Ciceri, P., Davis, M. I., Edeen, P. T., et al. (2008) · Nature Biotechnology · doi:10.1038/nbt1358 · Cited by 2,466
Kinase Mutations and Imatinib Response in Patients With Metastatic Gastrointestinal Stromal Tumor
Heinrich, M. C., Corless, C. L., Demetri, G. D., Blanke, C. D., von Mehren, M., Joensuu, H., McGreevey, L. S., Chen, C.-J., den Abbeele, A. D. V., Druker, B. J., et al. (2003) · Journal of Clinical Oncology · doi:10.1200/jco.2003.04.190 · Cited by 2,306
EGFR Antagonists in Cancer Treatment
Ciardiello, F., & Tortora, G. (2008) · New England Journal of Medicine · doi:10.1056/nejmra0707704 · Cited by 2,095
Phosphatidylinositol-3-OH kinase direct target of Ras
Rodriguez-Viciana, P., Warne, P. H., Dhand, R., Vanhaesebroeck, B., Gout, I., Fry, M. J., Waterfield, M. D., & Downward, J. (1994) · Nature · doi:10.1038/370527a0 · Cited by 1,954
A small molecule–kinase interaction map for clinical kinase inhibitors
Fabian, M. A., Biggs, W., Treiber, D. K., Atteridge, C. E., Azimioara, M. D., Benedetti, M. G., Carter, T. A., Ciceri, P., Edeen, P. T., Floyd, M. B., et al. (2005) · Nature Biotechnology · doi:10.1038/nbt1068 · Cited by 1,923
Cetuximab for the Treatment of Colorectal Cancer
Jonker, D. J., O'Callaghan, C. J., Karapetis, C. S., Zalcberg, J. R., Tu, D., Au, H.-J., Berry, S. R., Krahn, M., Price, T., Simes, R. J., et al. (2007) · New England Journal of Medicine · doi:10.1056/nejmoa071834 · Cited by 1,904
Skepinone-L, a Novel Potent and Highly Selective Inhibitor of p38 MAP Kinase, Effectively Impairs Platelet Activation and Thrombus Formation
Borst, O., Walker, B., Münzer, P., Russo, A., Schmid, E., Faggio, C., Bigalke, B., Laufer, S., Gawaz, M., & Lang, F. J. W. (2013) · Cellular Physiology and Biochemistry · doi:10.1159/000350110 · Cited by 1,867
Dasatinib in imatinib-resistant Philadelphia chromosome-positive leukemias
Talpaz, M., Shah, N. P., Kantarjian, H., Donato, N., Nicoll, J., Paquette, R., Cortes, J., O'Brien, S., Nicaise, C., Bleickardt, E., et al. (2006) · New England Journal of Medicine · doi:10.1056/nejmoa055229 · Cited by 1,760
A Tyrosine Kinase Created by Fusion of the PDGFRA and FIP1L1 Genes as a Therapeutic Target of Imatinib in Idiopathic Hypereosinophilic Syndrome
Cools, J., DeAngelo, D. J., Gotlib, J. R., Stover, E. H., Legare, R. D., Cortes, J. E., Kutok, J. L., Clark, J., Galinsky, I. A., Griffin, J. D., et al. (2003) · New England Journal of Medicine · doi:10.1056/nejmoa025217 · Cited by 1,714
Cetuximab in the treatment of colorectal cancer.
Goldberg, R. M., Venook, A. P., & Schilsky, R. L. (2004) · PubMed · Cited by 1,518
KRAS Mutations and Primary Resistance of Lung Adenocarcinomas to Gefitinib or Erlotinib
Pao, W. J., Wang, T. Y., Riely, G. J., Miller, V. A., Pan, Q., Ladanyi, M., Zakowski, M. F., Heelan, R. T., Kris, M. G., & VARMUS, H. E. (2005) · PLoS Medicine · doi:10.1371/journal.pmed.0020017 · Cited by 1,517
Molecular determinants of the response of glioblastomas to EGFR kinase inhibitors
Mellinghoff, I. K., Wang, M. Y., Vivanco, I., Haas-Kogan, D. A., Zhu, S., Dia, E. Q., Lu, K. V., Yoshimoto, K., Huang, J. H. Y., Chute, D. J., et al. (2005) · New England Journal of Medicine · doi:10.1056/nejmoa051918 · Cited by 1,442
Benefits of targeting both pericytes and endothelial cells in the tumor vasculature with kinase inhibitors
Bergers, G., Song, S., Meyer-Morse, N., Bergsland, E. K., & Hanahan, D. (2003) · Journal of Clinical Investigation · doi:10.1172/jci17929 · Cited by 1,361
Chemotherapy, Bevacizumab, and Cetuximab in Metastatic Colorectal Cancer
Tol, J., Koopman, M., Cats, A., Rodenburg, C. J., Creemers, G. J., Schrama, J. G., Erdkamp, F., Vos, A. H., van Groeningen, C. J., Sinnige, H. A. M., et al. (2009) · New England Journal of Medicine · doi:10.1056/nejmoa0808268 · Cited by 1,347
Nilotinib in Imatinib-Resistant CML and Philadelphia Chromosome–Positive ALL
Kantarjian, H. M., Giles, F. J., Wunderle, L., Bhalla, K. N., O'Brien, S. M., Waßmann, B., Tanaka, C., Manley, P. W., Rae, P., Mietlowski, W. L., et al. (2006) · New England Journal of Medicine · doi:10.1056/nejmoa055104 · Cited by 1,334
Effective use of PI3K and MEK inhibitors to treat mutant Kras G12D and PIK3CA H1047R murine lung cancers
Engelman, J. A., Chen, L., Tan, X., Crosby, K., Guimaraes, A. R., Upadhyay, R., Maira, M., McNamara, K., Perera, S. A., Song, Y., et al. (2008) · Nature Medicine · doi:10.1038/nm.1890 · Cited by 1,330
BRAF mutation predicts sensitivity to MEK inhibition
Solit, D. B., Garraway, L. A., Pratilas, C. A., Sawai, A., Getz, G. A., Basso, A., Ye, Q., Lobo, J. M., She, Y., Osman, I., et al. (2005) · Nature · doi:10.1038/nature04304 · Cited by 1,326
AP24534, a Pan-BCR-ABL Inhibitor for Chronic Myeloid Leukemia, Potently Inhibits the T315I Mutant and Overcomes Mutation-Based Resistance
O’Hare, T., Shakespeare, W. C., Zhu, X., Eide, C. A., Rivera, V. M., Wang, F., Adrian, L. T., Zhou, T., Huang, W.-S., Xu, Q., et al. (2009) · Cancer Cell · doi:10.1016/j.ccr.2009.09.028 · Cited by 1,296
Benefits of targeting both pericytes and endothelial cells in the tumor vasculature with kinase inhibitors
Bergers, G., Song, S., Meyer-Morse, N., et al. (2003) · Journal of Clinical Investigation · doi:10.1172/jci200317929 · Cited by 1,192
A Genome-wide RNAi Screen Identifies Multiple Synthetic Lethal Interactions with the Ras Oncogene
Luo, J., Emanuele, M. J., Li, D., Creighton, C. J., Schlabach, M. R., Westbrook, T. F., Wong, K.-K., & Elledge, S. J. (2009) · Cell · doi:10.1016/j.cell.2009.05.006 · Cited by 1,017
Escape from HER-family tyrosine kinase inhibitor therapy by the kinase-inactive HER3
Sergina, N. V., Rausch, M., Wang, D., Blair, J. A., Hann, B. C., Shokat, K. M., & Moasser, M. M. (2007) · Nature · doi:10.1038/nature05474 · Cited by 993
Coactivation of receptor tyrosine kinases affects the response of tumor cells to targeted therapies
Stommel, J. M., Kimmelman, A. C., Ying, H., Nabioullin, R., Ponugoti, A. H., Wiedemeyer, R., Stegh, A. H., Bradner, J. E., Ligon, K. L., Brennan, C., et al. (2007) · Science · doi:10.1126/science.1142946 · Cited by 938
Mutant PIK3CA promotes cell growth and invasion of human cancer cells.
Samuels, Y., Diaz, L. A., Schmidt-Kittler, O., Cummins, J. M., DeLong, L., Cheong, I., Rago, C., Huso, D. L., Lengauer, C., Kinzler, K. W., et al. (2005) · Cancer Cell · doi:10.1016/j.ccr.2005.05.014 · Cited by 915
Ligand-Independent HER2/HER3/PI3K Complex Is Disrupted by Trastuzumab and Is Effectively Inhibited by the PI3K Inhibitor GDC-0941
Junttila, T. T., Akita, R. W., Parsons, K. L., Fields, C. T., Phillips, G. D. L., Friedman, L. S., Sampath, D., & Sliwkowski, M. X. (2009) · Cancer Cell · doi:10.1016/j.ccr.2009.03.020 · Cited by 848
Features of Selective Kinase Inhibitors
Knight, Z. A., & Shokat, K. M. (2005) · Chemistry & Biology · doi:10.1016/j.chembiol.2005.04.011 · Cited by 676
Differential effects of oncogenic K-Ras and N-Ras on proliferation, differentiation and tumor progression in the colon
Haigis, K. M., Kendall, K. R., Wang, Y., Cheung, A., Haigis, M. C., Glickman, J. N., Niwa-Kawakita, M., Sweet-Cordero, A., Sebolt-Leopold, J., Shannon, K. M., et al. (2008) · Nature Genetics · doi:10.1038/ng.115 · Cited by 610
Binding of Ras to Phosphoinositide 3-Kinase p110α Is Required for Ras- Driven Tumorigenesis in Mice
Gupta, S., Ramjaun, A. R., Haiko, P., Wang, Y., Warne, P. H., Nicke, B., Nye, E. L., Stamp, G., Alitalo, K. K., & Downward, J. (2007) · Cell · doi:10.1016/j.cell.2007.03.051 · Cited by 603
Mutations in a signalling pathway
Parsons, D. W., Wang, T., Samuels, Y., Bardelli, A., Cummins, J. M., Wood, L. D., Silliman, N., Ptak, J., Szabo, S., Willson, J. K. V., et al. (2005) · Nature · doi:10.1038/436792a · Cited by 599
A dual PI3 kinase/mTOR inhibitor reveals emergent efficacy in glioma
Fan, Q.-W., Knight, Z. A., Goldenberg, D., Yu, W., Mostov, K. E., Stokoe, D., Shokat, K. M., & Weiss, W. A. (2006) · Cancer Cell · doi:10.1016/j.ccr.2006.03.029 · Cited by 584
Inhibition of drug-resistant mutants of ABL, KIT, and EGF receptor kinases
Carter, T. A., Wodicka, L. M., Shah, N. P., Velasco, A. M., Fabian, M. A., Treiber, D. K., Milanov, Z. V., Atteridge, C. E., Biggs, W., Edeen, P. T., et al. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0504952102 · Cited by 555
Results of a Phase III, Randomized, Placebo-Controlled Study of Sorafenib in Combination With Carboplatin and Paclitaxel As Second-Line Treatment in Patients With Unresectable Stage III or Stage IV Melanoma
Hauschild, A., Agarwala, S. S., Trefzer, U., Hogg, D., Robert, C., Hersey, P., Eggermont, A. M. M., Grabbe, S., Gonzalez, R. C., Gille, J., et al. (2009) · Journal of Clinical Oncology · doi:10.1200/jco.2007.15.7636 · Cited by 548
Epidermal growth factor receptor (HER1) tyrosine kinase inhibitor ZD1839 (Iressa) inhibits HER2/neu (erbB2)-overexpressing breast cancer cells in vitro and in vivo.
Moulder, S. L., Yakes, F. M., Muthuswamy, S. K., Bianco, R., Simpson, J. F., & Arteaga, C. L. (2001) · PubMed · Cited by 548
Synthetic Lethal Interaction between Oncogenic KRAS Dependency and STK33 Suppression in Human Cancer Cells
Scholl, C., Fröhling, S., Dunn, I. F., Schinzel, A. C., Barbie, D. A., Kim, S. Y., Silver, S. J., Tamayo, P., Wadlow, R. C., Ramaswamy, S., et al. (2009) · Cell · doi:10.1016/j.cell.2009.03.017 · Cited by 546
Requirement for NF-κB signalling in a mouse model of lung adenocarcinoma
Meylan, E., Dooley, A. L., Feldser, D. M., Shen, L., Turk, E., Ouyang, C., & Jacks, T. (2009) · Nature · doi:10.1038/nature08462 · Cited by 514
Phosphatidylinositol 3-kinase hyperactivation results in lapatinib resistance that is reversed by the mTOR/phosphatidylinositol 3-kinase inhibitor NVP-BEZ235
Eichhorn, P. J. A., Gili, M., Scaltriti, M., Serra, V., Guzman, M., Nijkamp, W., Beijersbergen, R. L., Valero, V., Seoane, J., Bernards, R., et al. (2008) · Cancer Research · doi:10.1158/0008-5472.can-08-1740 · Cited by 499
Can we rationally design promiscuous drugs?
HOPKINS, A., MASON, J., & OVERINGTON, J. (2006) · Current Opinion in Structural Biology · doi:10.1016/j.sbi.2006.01.013 · Cited by 469
Targeted polypharmacology: discovery of dual inhibitors of tyrosine and phosphoinositide kinases
Apsel, B., Blair, J. A., González, B., Nazif, T. M., Feldman, M. E., Aizenstein, B., Hoffman, R., Williams, R. L., Shokat, K. M., & Knight, Z. A. (2008) · Nature Chemical Biology · doi:10.1038/nchembio.117 · Cited by 460
PI3K Pathway Activation Mediates Resistance to MEK Inhibitors in KRAS Mutant Cancers
Wee, S., Jagani, Z., Xiang, K. X., Loo, A., Dorsch, M., Yao, Y.-M., Sellers, W. R., Lengauer, C., & Stegmeier, F. (2009) · Cancer Research · doi:10.1158/0008-5472.can-08-4765 · Cited by 455
Sequential ABL kinase inhibitor therapy selects for compound drug-resistant BCR-ABL mutations with altered oncogenic potency
Shah, N. P., Skaggs, B. J., Branford, S., Hughes, T. P., Nicoll, J. M., PAQUETTE, R. L., & Sawyers, C. L. (2007) · Journal of Clinical Investigation · doi:10.1172/jci30890 · Cited by 411
Discovery of a novel Raf kinase inhibitor.
Lyons, J. F., Wilhelm, S. M., Hibner, B., & Bollag, G. E. (2001) · Endocrine Related Cancer · doi:10.1677/erc.0.0080219 · Cited by 410
A systematic interaction map of validated kinase inhibitors with Ser/Thr kinases
Fedorov, O., Marsden, B. D., Pogačić, V., Rellos, P., Müller, S., Bullock, A. N., Schwaller, J., Sundström, M., & Knapp, S. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0708800104 · Cited by 362
MK-0457, a novel kinase inhibitor, is active in patients with chronic myeloid leukemia or acute lymphocytic leukemia with the T315I BCR-ABL mutation
Giles, F. J., Cortes, J. E., Jones, D. M., Bergstrom, D. A., Kantarjian, H. M., & Freedman, S. J. (2006) · Blood · doi:10.1182/blood-2006-05-025049 · Cited by 361
Identification of genotype-correlated sensitivity to selective kinase inhibitors by using high-throughput tumor cell line profiling
McDermott, U., Sharma, S. V., Dowell, L., Greninger, P., Montagut, C. O., Lamb, J. A., Archibald, H., Raudales, R., Tam, A., Lee, D. W., et al. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0707498104 · Cited by 352
A Missense Mutation in KIT Kinase Domain 1 Correlates with Imatinib Resistance in Gastrointestinal Stromal Tumors
Chen, L. L., Trent, J. C., Wu, E. F., Fuller, G. N., Ramdas, L., Zhang, W., Raymond, A. K., Prieto, V. G., Oyedeji, C. O., Hunt, K. K., et al. (2004) · Cancer Research · doi:10.1158/0008-5472.can-04-0085 · Cited by 338
A new mutation in the KIT ATP pocket causes acquired resistance to imatinib in a gastrointestinal stromal tumor patient
Tamborini, E., Bonadiman, L., Greco, A., Albertini, V., Negri, T., Gronchi, A., Bertulli, R., Colecchia, M., Casali, P. G., Pierotti, M. A., et al. (2004) · Gastroenterology · doi:10.1053/j.gastro.2004.02.021 · Cited by 323
Randomized Phase II Study of Erlotinib Combined With Bevacizumab Compared With Bevacizumab Alone in Metastatic Renal Cell Cancer
Bukowski, R. M., Kabbinavar, F. F., Figlin, R. A., Flaherty, K. T., Srinivas, S., Vaishampayan, U. N., Drabkin, H. A., Dutcher, J. P., Ryba, S., Xia, Q., et al. (2007) · Journal of Clinical Oncology · doi:10.1200/jco.2007.11.5154 · Cited by 314
Treatment of hypereosinophilic syndrome with imatinib mesilate
Gleich, G. J., Leiferman, K. M., Pardanani, A. D., Tefferi, A., & Butterfield, J. H. (2002) · The Lancet · doi:10.1016/s0140-6736(02)08505-7 · Cited by 303
Renewing the conspiracy theory debate: does Raf function alone to mediate Ras oncogenesis?
Repasky, G. A., Chenette, E. J., & Der, C. J. (2004) · Trends in Cell Biology · doi:10.1016/j.tcb.2004.09.014 · Cited by 299
Cooperative inhibitory effect of ZD1839 (Iressa) in combination with trastuzumab (Herceptin) on human breast cancer cell growth
Normanno, N., Campiglio, M., Luca, A. D., Somenzi, G., Maiello, M. R., Ciardiello, F., Gianni, L., Salomon, D. S., & Ménard, S. (2002) · Annals of Oncology · doi:10.1093/annonc/mdf020 · Cited by 272
Chemical genetics: where genetics and pharmacology meet.
Knight, Z. A., & Shokat, K. (2007) · Cell · doi:10.1016/j.cell.2007.01.021 · Cited by 242
Potent and selective inhibitors of Akt kinases slow the progress of tumors in vivo
Luo, Y., Shoemaker, A. R., Liu, X., Woods, K. W., Thomas, S. A., de Jong, R., Han, E. K.-H., Li, T., Stoll, V. S., Powlas, J. A., et al. (2005) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-05-0005 · Cited by 233
Transient Potent BCR-ABL Inhibition Is Sufficient to Commit Chronic Myeloid Leukemia Cells Irreversibly to Apoptosis
Shah, N. P., Kasap, C., Weier, C. A., Balbas, M., Nicoll, J. M., Bleickardt, E. W., Nicaise, C., & Sawyers, C. L. (2008) · Cancer Cell · doi:10.1016/j.ccr.2008.11.001 · Cited by 231
Use of isogenic human cancer cells for high-throughput screening and drug discovery
Torrance, C. J., Agrawal, V., Vogelstein, B., & Kinzler, K. W. (2001) · Nature Biotechnology · doi:10.1038/nbt1001-940 · Cited by 228
A Dual Phosphoinositide-3-Kinase α/mTOR Inhibitor Cooperates with Blockade of Epidermal Growth Factor Receptor in PTEN -Mutant Glioma
Fan, Q.-W., Cheng, C. K., Nicolaides, T. P., Hackett, C. S., Knight, Z. A., Shokat, K. M., & Weiss, W. A. (2007) · Cancer Research · doi:10.1158/0008-5472.can-07-2154 · Cited by 192
Target Identification in Chemical Genetics
Burdine, L. J., & Kodadek, T. J. (2004) · Chemistry & Biology · doi:10.1016/j.chembiol.2004.05.001 · Cited by 191
Simultaneous targeting of Aurora kinases and Bcr-Abl kinase by the small molecule inhibitor PHA-739358 is effective against imatinib-resistant BCR-ABL mutations including T315I
Gontarewicz, A., Balabanov, S., Keller, G., Colombo, R., Graziano, A., Pesenti, E. A., Benten, D., Bokemeyer, C., Fiedler, W., Moll, J. K., et al. (2008) · Blood · doi:10.1182/blood-2007-09-113175 · Cited by 166
Assessment of Chemical Coverage of Kinome Space and Its Implications for Kinase Drug Discovery
Bamborough, P., Drewry, D. H., Harper, G., Smith, G. K., & Schneider, K. (2008) · Journal of Medicinal Chemistry · doi:10.1021/jm8011036 · Cited by 161
Synergistic Antitumor Effects of Combined Epidermal Growth Factor Receptor and Vascular Endothelial Growth Factor Receptor-2 Targeted Therapy
Tonra, J. R., Deevi, D. S., Corcoran, E., Li, H., Wang, S., Carrick, F. E., & Hicklin, D. J. (2006) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-05-1682 · Cited by 151
Disorders in cell circuitry associated with multistage carcinogenesis: exploitable targets for cancer prevention and therapy.
Weinstein, I. B., Begemann, M., Zhou, P., Han, E. K.-H., Sgambato, A., Doki, Y., Arber, N., Ciaparrone, M., & Yamamoto, H. (1997) · PubMed · Cited by 125
Augmentation of apoptosis and tumor regression by flavopiridol in the presence of CPT-11 in Hct116 colon cancer monolayers and xenografts.
Motwani, M., Jung, C. P., Sirotnak, F. M., She, Y., Shah, M. A., Gönen, M., & Schwartz, G. K. (2001) · PubMed · Cited by 116
Kinase-targeted libraries: The design and synthesis of novel, potent, and selective kinase inhibitors
Akritopoulou‐Zanze, I., & Hajduk, P. J. (2009) · Drug Discovery Today · doi:10.1016/j.drudis.2008.12.002 · Cited by 116
Results of phase I pharmacokinetic and pharmacodynamic studies of the Raf kinase inhibitor BAY 43-9006 in patients with solid tumors
Strumberg, D., Voliotis, D., Moeller, J.-G., Hilger, R. A., Richly, H., Kredtke, S., Beling, C., Scheulen, M. E., & Seeber, S. (2002) · International Journal of Clinical Pharmacology and Therapeutics · doi:10.5414/cpp40580 · Cited by 104
A Phase I Clinical Trial of the Sequential Combination of Irinotecan Followed by Flavopiridol
Shah, M. A., Kortmansky, J. S., Motwani, M., Drobnjak, M., Gönen, M., Yi, S., Weyerbacher, A. R., Cordon‐Cardo, C., Lefkowitz, R. A., Brenner, B., et al. (2005) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-04-2651 · Cited by 101
Kinase requirements in human cells: I. Comparing kinase requirements across various cell types
Grueneberg, D. A., Degot, S., Pearlberg, J., Li, W., Davies, J. E., Baldwin, A. E., Endege, W. O., Doench, J. G., Sawyer, J., Hu, Y., et al. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0808019105 · Cited by 88
Treatment of HER-2/ neu Overexpressing Breast Cancer Xenograft Models with Trastuzumab (Herceptin) and Gefitinib (ZD1839): Drug Combination Effects on Tumor Growth, HER-2/ neu and Epidermal Growth Factor Receptor Expression, and Viable Hypoxic Cell Fraction
Warburton, C., Dragowska, W. H., Gelmon, K. A., Chia, S., Yan, H., Masin, D., Denyssevych, T., Wallis, A. E., & Bally, M. B. (2004) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-03-0244 · Cited by 83
SGX393 inhibits the CML mutant Bcr-Abl T315I and preempts in vitro resistance when combined with nilotinib or dasatinib
O’Hare, T., Eide, C. A., Tyner, J. W., Corbin, A. S., Wong, M. J., Buchanan, S. G., Holme, K. R., Jessen, K. A., Tang, C. M., Lewis, H. A., et al. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0800587105 · Cited by 81
A Phase I-II Study of Combined Blockade of the ErbB Receptor Network with Trastuzumab and Gefitinib in Patients with HER2 (ErbB2)-Overexpressing Metastatic Breast Cancer
Arteaga, C. L., O’Neill, A., Moulder, S. L., Pins, M., Sparano, J. A., Sledge, G. W., & Davidson, N. E. (2008) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-08-0482 · Cited by 79
Challenges and Opportunities in Defining the Essential Cancer Kinome
Manning, B. D. (2009) · Science Signaling · doi:10.1126/scisignal.263pe15 · Cited by 59
Mixing cocktails
Sawyers, C. L. (2007) · Nature · doi:10.1038/449993a · Cited by 59
RNAi-based screening of the human kinome identifies Akt-cooperating kinases: a new approach to designing efficacious multitargeted kinase inhibitors
Morgan-Lappe, S. E., Woods, K. W., Li, Q., Anderson, M. G., Schurdak, M. E., Luo, Y., Giranda, V. L., Fesik, S. W., & Leverson, J. D. (2005) · Oncogene · doi:10.1038/sj.onc.1209169 · Cited by 53
Kinase requirements in human cells: II. Genetic interaction screens identify kinase requirements following HPV16 E7 expression in cancer cells
Baldwin, A. E., Li, W., Grace, M. R., Pearlberg, J., Harlow, E., Münger, K., & Grueneberg, D. A. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0806195105 · Cited by 46
For Investigational Targeted Drugs, Combination Trials Pose Challenges
Goldman, B. (2003) · JNCI Journal of the National Cancer Institute · doi:10.1093/jnci/95.23.1744 · Cited by 15
Is the gefitinib plus trastuzumab combination feasible in breast cancer patients?
Normanno, N., Campiglio, M., Perrone, F., Luca, A. D., & Ménard, S. (2005) · Annals of Oncology · doi:10.1093/annonc/mdi325 · Cited by 11
History and Accomplishments of the Inter-Company Collaboration for Aids Drug Development
Barry, D. W., & Distlerath, L. M. (2000) · Drug Information Journal · doi:10.1177/009286150003400310 · Cited by 3
Optimising strategies for clinical development of combinations of targeted agents
Chen, H. (2007) · European Journal of Cancer Supplements · doi:10.1016/j.ejcsup.2007.09.030 · Cited by 1

Flagged first, then by citations

4 of the 104 references couldn’t be matched to a known paper.

Research works printed but not linked: 1

Winslow, R. AstraZeneca, Merck to Test Cancer Drugs in 'Cocktail'. The Wall Street Journal [online] , (2009).

Sorted by citations

Comprehensive analysis of kinase inhibitor selectivity
Davis, M. I., Hunt, J. P., Herrgard, S., Ciceri, P., Wodicka, L. M., Pallares, G., Hocker, M., Treiber, D. K., & Zarrinkar, P. P. (2011) · Nature Biotechnology · doi:10.1038/nbt.1990 · Cited by 2,409
“The assay panels further have enabled a novel approach to kinase inhibitor discovery, based on screening entire libraries of compounds against panels of kinases, which has resulted in the discovery of several promising new inhibitor”
Background
The ErbB/HER family of protein-tyrosine kinases and cancer
Roskoski, R. J. (2013) · Pharmacological Research · doi:10.1016/j.phrs.2013.11.002 · Cited by 1,408
Kinase-targeted cancer therapies: progress, challenges and future directions
Bhullar, K. S., Orrego-Lagarón, N., McGowan, E. M., Parmar, I., Jha, A., Hubbard, B. P., & Rupasinghe, H. P. V. (2018) · Molecular Cancer · doi:10.1186/s12943-018-0804-2 · Cited by 1,316
“Further, in some cases, the combinations of kinase targeting agents reduced patient survival compared with the treatment using single drug [281].”
Background
Target identification and mechanism of action in chemical biology and drug discovery
Schenone, M., Dančík, V., Wagner, B. K., & Clemons, P. A. (2013) · Nature Chemical Biology · doi:10.1038/nchembio.1199 · Cited by 1,147
Polypharmacology: Challenges and Opportunities in Drug Discovery: Miniperspective
Anighoro, A., Bajorath, J., & Rastelli, G. (2014) · Journal of Medicinal Chemistry · doi:10.1021/jm5006463 · Cited by 1,131

See all 714

Authors: Knight, Z. A., Lin, H., & Shokat, K. M.
Affiliations: Rockefeller University (US)
Howard Hughes Medical Institute (US)
Corresponding author: Knight, Zachary A.
Shokat, Kevan M.
ORCID: Knight, Zachary A.
Shokat, Kevan M.
Venue: Nature reviews. Cancer
Publisher: Springer Science and Business Media LLC
Published: 2010-02
Volume: 10
Issue: 2
Pages: 130-137
ISSN: 1474-175X (ISSN-L)
1474-1768
DOI: 10.1038/nrc2787
PMC: PMC2880454
OpenAlex: W2022609682
Cited by: 674
References: 104
Citations by year: 2026: 17 · 2025: 20 · 2024: 21 · 2023: 22 · 2022: 24 · 2021: 29 · 2020: 47 · 2019: 34 · 2018: 45 · 2017: 51 · 2016: 43 · 2015: 48 · 2014: 72 · 2013: 70 · 2012: 43
FWCI: 8.19
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: www.springer.com/tdm (tdm)
Locations: Nature reviews. Cancer (publishedVersion)
PubMed (publishedVersion)
PubMed Central (acceptedVersion)
Funders: Howard Hughes Medical Institute
National Institutes of Health (5r01eb001987-15)
National Institute of Diabetes and Digestive and Kidney Diseases (R00DK083531, K99DK083531)
National Institute of Biomedical Imaging and Bioengineering (R01-EB001987)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer Mechanisms and Therapy
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Drug Discovery › Computational Drug Discovery Methods
Keywords: kinase inhibitors, polypharmacology, combination therapy, drug resistance, anticancer drug development
MeSH terms: Antineoplastic Agents, Antineoplastic Combined Chemotherapy Protocols, Humans, Mutation, Neoplasms, Protein Kinases, Technology, Pharmaceutical, Drug Delivery Systems, Drug Resistance, Neoplasm, RNA, Small Interfering, Protein Kinase Inhibitors, Drug Discovery

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review

Targeting the cancer kinome through polypharmacology

Abstract

Overview

Integrity signals

Verification

Claims the paper makes

Claims other papers make about this one

Self-check

Citations

Cites

Cited by

Related

Metadata

Record

About these checks