Targeting the MAPK pathway in KRAS-driven tumors

The Clinical KRAS(G12C) Inhibitor AMG 510 Drives Anti-Tumour Immunity

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RAS oncogenes: the first 30 years

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Discovery and development of sorafenib: a multikinase inhibitor for treating cancer

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RAF inhibitors transactivate RAF dimers and ERK signalling in cells with wild-type BRAF

Poulikakos, P. I., Zhang, C., Bollag, G. E., Shokat, K. M., & Rosen, N. X. (2010) · Nature · doi:10.1038/nature08902 · Cited by 1,818 · see citing works

RAF inhibitors prime wild-type RAF to activate the MAPK pathway and enhance growth

Hatzivassiliou, G., Song, K. W., Yen, I., Brandhuber, B. J., Anderson, D. J., Alvarado, R., Ludlam, M. J. C., Stokoe, D., Gloor, S. L., Vigers, G. P. A., et al. (2010) · Nature · doi:10.1038/nature08833 · Cited by 1,614 · see citing works

Kinase-Dead BRAF and Oncogenic RAS Cooperate to Drive Tumor Progression through CRAF

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The KRASG12C Inhibitor MRTX849 Provides Insight toward Therapeutic Susceptibility of KRAS-Mutant Cancers in Mouse Models and Patients

Hallin, J., Engstrom, L. D., Hargis, L., Calinisan, A., Aranda, R., Briere, D. M., Sudhakar, N., Bowcut, V., Baer, B. R., Ballard, J. A., et al. (2020) · Cancer Discovery · doi:10.1158/2159-8290.cd-19-1167 · Cited by 1,304 · see citing works

Targeting RAS–ERK signalling in cancer: promises and challenges

Samatar, A. A., & Poulikakos, P. I. (2014) · Nature Reviews Drug Discovery · doi:10.1038/nrd4281 · Cited by 1,163 · see citing works

The BATTLE Trial: Personalizing Therapy for Lung Cancer

Kim, E. S., Herbst, R. S., Wistuba, I. I., Lee, J. J., Blumenschein, G. R., Tsao, A. S., Stewart, D. J., Hicks, M. E., Erasmus, J. J., Gupta, S. K., et al. (2011) · Cancer Discovery · doi:10.1158/2159-8274.cd-10-0010 · Cited by 888 · see citing works

Bcl-2 Targets the Protein Kinase Raf-1 to Mitochondria

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Combination of ERK and autophagy inhibition as a treatment approach for pancreatic cancer

Bryant, K. L., Stalnecker, C. A., Zeitouni, D., Klomp, J. E., Peng, S., Tikunov, A. P., Gunda, V., Pierobon, M., Waters, A. M., George, S. D., et al. (2019) · Nature Medicine · doi:10.1038/s41591-019-0368-8 · Cited by 692 · see citing works

Regulation of RAF protein kinases in ERK signalling

Lavoie, H., & Therrien, M. (2015) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3979 · Cited by 683 · see citing works

Protective autophagy elicited by RAF→MEK→ERK inhibition suggests a treatment strategy for RAS-driven cancers

Kinsey, C. G., Camolotto, S. A., Boespflug, A. M., Guillen, K. P., Foth, M., Truong, A., Schuman, S. S., Shea, J. E., Seipp, M. T., Yap, J. T., et al. (2019) · Nature Medicine · doi:10.1038/s41591-019-0367-9 · Cited by 634 · see citing works

Signalling ballet in space and time

Kholodenko, B. Ν., Hancock, J. F., & Kölch, W. (2010) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2901 · Cited by 618 · see citing works

Negative feedback regulation of the ERK1/2 MAPK pathway

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Tumours with class 3 BRAF mutants are sensitive to the inhibition of activated RAS

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Safety, pharmacokinetic, pharmacodynamic, and efficacy data for the oral MEK inhibitor trametinib: a phase 1 dose-escalation trial.

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EGF Receptor is Required for KRAS-induced Pancreatic Tumorigenesis

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Regulation and Functions of Rho-Associated Kinase

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Targeting Alterations in the RAF–MEK Pathway

Yaeger, R. D., & Corcoran, R. B. (2019) · Cancer Discovery · doi:10.1158/2159-8290.cd-18-1321 · Cited by 477 · see citing works

Therapeutic strategies to target RAS-mutant cancers

Ryan, M. B., & Corcoran, R. B. (2018) · Nature Reviews Clinical Oncology · doi:10.1038/s41571-018-0105-0 · Cited by 420 · see citing works

EGF Receptor Signaling Is Essential for K-Ras Oncogene-Driven Pancreatic Ductal Adenocarcinoma

Navas, C., Hernández-Porras, I., Schuhmacher, A. J., Sibilia, M., Guerra, C., & Barbacid, M. (2012) · Cancer Cell · doi:10.1016/j.ccr.2012.08.001 · Cited by 391 · see citing works

Discovery of potent SOS1 inhibitors that block RAS activation via disruption of the RAS–SOS1 interaction

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RAF inhibitors that evade paradoxical MAPK pathway activation

Zhang, C., Spevak, W. R., Zhang, Y., Burton, E. A., Ma, Y., Habets, G. G. M., Zhang, J., Lin, J. Y.-S., Ewing, T. J. A., Matusow, B., et al. (2015) · Nature · doi:10.1038/nature14982 · Cited by 383 · see citing works

RAF protein-serine/threonine kinases: Structure and regulation

Roskoski, R. J. (2010) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2010.07.092 · Cited by 372 · see citing works

A randomised, double-blind, placebo-controlled trial of trametinib, an oral MEK inhibitor, in combination with gemcitabine for patients with untreated metastatic adenocarcinoma of the pancreas

Infante, J. R., Somer, B. G., Park, J. O., Li, C., Scheulen, M. E., Kasubhai, S. M., Oh, D., Liu, Y., Redhu, S., Steplewski, K. M., et al. (2014) · European Journal of Cancer · doi:10.1016/j.ejca.2014.04.024 · Cited by 370 · see citing works

Mutant KRAS-driven cancers depend on PTPN11/SHP2 phosphatase

Ruess, D. A., Heynen, G. J., Ciecielski, K. J., Ai, J., Berninger, A., Kabacaoglu, D., Görgülü, K., Dantes, Z., Wörmann, S. M., Diakopoulos, K. N., et al. (2018) · Nature Medicine · doi:10.1038/s41591-018-0024-8 · Cited by 370 · see citing works

An essential function of the mitogen‐activated protein kinase Erk2 in mouse trophoblast development

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Selective requirement of PI3K/PDK1 signaling for Kras oncogene-driven pancreatic cell plasticity and cancer

Eser, S., Reiff, N., Messer, M., Seidler, B., Gottschalk, K., Dobler, M., Hieber, M., Arbeiter, A., Klein, S., Kong, B., et al. (2013) · Cancer Cell · doi:10.1016/j.ccr.2013.01.023 · Cited by 360 · see citing works

A randomized phase II study of the MEK1/MEK2 inhibitor trametinib (GSK1120212) compared with docetaxel in KRAS-mutant advanced non-small-cell lung cancer (NSCLC)

Blumenschein, G. R., Smit, E. F., Planchard, D., Kim, D.-W., Cadranel, J., De Pas, T., Dunphy, F., Udud, K., Ahn, M.-J., Hanna, N. H., et al. (2015) · Annals of Oncology · doi:10.1093/annonc/mdv072 · Cited by 349 · see citing works

Embryonic death of Mek1-deficient mice reveals a role for this kinase in angiogenesis in the labyrinthine region of the placenta

Giroux, S., Tremblay, M. G., Bernard, D., Cardin-Girard, J.-F., Aubry, S., Larouche, L., Rousseau, S., Huot, J. L., Landry, J., Jeannotte, L., et al. (1999) · Current Biology · doi:10.1016/s0960-9822(99)80164-x · Cited by 342 · see citing works

Selumetinib Plus Docetaxel Compared With Docetaxel Alone and Progression-Free Survival in Patients With <i>KRAS</i> -Mutant Advanced Non–Small Cell Lung Cancer: The SELECT-1 Randomized Clinical Trial

Jänne, P. A., van den Heuvel, M. M., Barlesi, F., Cobo, M., Mazieres, J., Crinò, L., Orlov, S., Blackhall, F., Wolf, J., Garrido, P., et al. (2017) · JAMA · doi:10.1001/jama.2017.3438 · Cited by 335 · see citing works

SHP2 is required for growth of KRAS-mutant non-small-cell lung cancer in vivo

Mainardi, S., Mulero-Sánchez, A., Prahallad, A., Germano, G., Bosma, A., Krimpenfort, P., Lieftink, C., Steinberg, J. D., de Wit, N., Gonçalves-Ribeiro, S., et al. (2018) · Nature Medicine · doi:10.1038/s41591-018-0023-9 · Cited by 320 · see citing works

Role of the Kinase MST2 in Suppression of Apoptosis by the Proto-Oncogene Product Raf-1

O’Neill, E. E., Rushworth, L. K., Baccarini, M., & Kölch, W. (2004) · Science · doi:10.1126/science.1103233 · Cited by 317 · see citing works

Raf-1 promotes cell survival by antagonizing apoptosis signal-regulating kinase 1 through a MEK–ERK independent mechanism

Chen, J., Fujii, K., Zhang, L., Roberts, T. M., & Fu, H. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.141224398 · Cited by 316 · see citing works

Embryonic lethality and fetal liver apoptosis in mice lacking the c‐raf‐1 gene

Mikula, M., Schreiber, M., Husak, Z., Kučerová, L., Rüth, J., Wieser, R., Zatloukal, K., Beug, H., Wagner, E. F., & Baccarini, M. (2001) · The EMBO Journal · doi:10.1093/emboj/20.8.1952 · Cited by 311 · see citing works

MEK kinase activity is not necessary for Raf‐1 function

Hüser, M., Luckett, J., Chiloeches, A., Mercer, K., Iwobi, M., Giblett, S., Sun, X., Brown, J., Marais, R., & Pritchard, C. A. (2001) · The EMBO Journal · doi:10.1093/emboj/20.8.1940 · Cited by 310 · see citing works

c-Raf, but not B-Raf, is essential for development of K-Ras oncogene-driven non-small cell lung carcinoma

Blasco, R. B., Francoz, S., Santamaría, D., Cañamero, M., Dubus, P., Charron, J., Baccarini, M., & Barbacid, M. (2011) · Cancer Cell · doi:10.1016/j.ccr.2011.04.002 · Cited by 302 · see citing works

Endothelial apoptosis in Braf-deficient mice

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Essential role for ERK2 mitogen‐activated protein kinase in placental development

Hatano, N., Mori, Y., Oh‐hora, M., Kosugi, A., Fujikawa, T., Nakai, N., Niwa, H., Miyazaki, J., Hamaoka, T., & Ogata, M. (2003) · Genes to Cells · doi:10.1046/j.1365-2443.2003.00680.x · Cited by 296 · see citing works

A Small Molecule RAS-Mimetic Disrupts RAS Association with Effector Proteins to Block Signaling

Divakar, S. K. A., Carpio, R. V., Dutta, K., Baker, S. J., Cosenza, S. C., Basu, I., Gupta, Y. K., Reddy, M. V. R., Ueno, L. A., Hart, J. R., et al. (2016) · Cell · doi:10.1016/j.cell.2016.03.045 · Cited by 278 · see citing works

MEK1/2 dual-specificity protein kinases: Structure and regulation

Roskoski, R. J. (2011) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2011.11.145 · Cited by 277 · see citing works

Skin toxicities associated with epidermal growth factor receptor inhibitors

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Combined CRISPRi/a-Based Chemical Genetic Screens Reveal that Rigosertib Is a Microtubule-Destabilizing Agent

Jost, M., Chen, Y., Gilbert, L. A., Horlbeck, M. A., Krenning, L., Menchon, G., Rai, A., Cho, M. Y., Stern, J. J., Prota, A. E., et al. (2017) · Molecular Cell · doi:10.1016/j.molcel.2017.09.012 · Cited by 241 · see citing works

A Phase II Study of PD-0325901, an Oral MEK Inhibitor, in Previously Treated Patients with Advanced Non–Small Cell Lung Cancer

Haura, E. B., Ricart, A. D., Larson, T. G., Stella, P. J., Bazhenova, L., Miller, V. A., Cohen, R. B., Eisenberg, P. D., Selaru, P., Wilner, K. D., et al. (2010) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-09-1920 · Cited by 237 · see citing works

A phase II open-label randomized study to assess the efficacy and safety of selumetinib (AZD6244 [ARRY-142886]) versus capecitabine in patients with advanced or metastatic pancreatic cancer who have failed first-line gemcitabine therapy

Bodoky, G., Timcheva, C., Spigel, D. R., La Stella, P. J., Ciuleanu, T. E., Pover, G., & Tebbutt, N. C. (2012) · Investigational New Drugs · doi:10.1007/s10637-011-9687-4 · Cited by 236 · see citing works

PROTACs: An Emerging Targeting Technique for Protein Degradation in Drug Discovery

Gu, S., Cui, D., Chen, X., Xiong, X., & Zhao, Y. (2018) · BioEssays · doi:10.1002/bies.201700247 · Cited by 231 · see citing works

Raf-1 regulates Rho signaling and cell migration

Ehrenreiter, K., Piazzolla, D., Velamoor, V., Sobczak, I., Small, J. V., Takeda, J., LEUNG, T. K. C., & Baccarini, M. (2005) · The Journal of Cell Biology · doi:10.1083/jcb.200409162 · Cited by 207 · see citing works

Raf-1 protein kinase activates the NF-kappa B transcription factor by dissociating the cytoplasmic NF-kappa B-I kappa B complex.

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RAF inhibitor PLX8394 selectively disrupts BRAF dimers and RAS-independent BRAF-mutant-driven signaling

Yao, Z., Gao, Y., Su, W., Yaeger, R., Tao, J., Na, N., Zhang, Y., Zhang, C., Rymar, A., Tao, A., et al. (2019) · Nature Medicine · doi:10.1038/s41591-018-0274-5 · Cited by 195 · see citing works

Ras-Mediated Activation of the Raf Family KinasesPreprint

Terrell, E. M., & Morrison, D. K. (2018) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a033746 · Cited by 189 · see citing works

Targeting the ERK Signaling Pathway in Melanoma

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A Mek1–Mek2 heterodimer determines the strength and duration of the Erk signal

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A compendium of ERK targets

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Mek2 Is Dispensable for Mouse Growth and Development

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Raf induces NF-κB by membrane shuttle kinase MEKK1, a signaling pathway critical for transformation

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An approach to suppress the evolution of resistance in BRAFV600E-mutant cancer

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MEK Guards Proteome Stability and Inhibits Tumor-Suppressive Amyloidogenesis via HSF1

Tang, Z., Dai, S., He, Y., Doty, R. A., Shultz, L. D., Sampson, S. B., & Dai, C. (2015) · Cell · doi:10.1016/j.cell.2015.01.028 · Cited by 168 · see citing works

Post-natal lethality and neurological and gastrointestinal defects in mice with targeted disruption of the A-Raf protein kinase gene

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C-Raf Is Required for the Initiation of Lung Cancer by K-RasG12D

Karreth, F. A., Frese, K. K., DeNicola, G. M., Baccarini, M., & Tuveson, D. A. (2011) · Cancer Discovery · doi:10.1158/2159-8290.cd-10-0044 · Cited by 149 · see citing works

Small Molecule Inhibition of ERK Dimerization Prevents Tumorigenesis by RAS-ERK Pathway Oncogenes

Herrero, A., Pinto, A., Colón‐Bolea, P., Casar, B., Jones, M., Agudo‐Ibáñez, L., Vidal, R., Tenbaum, S. P., Nuciforo, P. G., Valdizán, E. M., et al. (2015) · Cancer Cell · doi:10.1016/j.ccell.2015.07.001 · Cited by 148 · see citing works

Mek1/2 MAPK Kinases Are Essential for Mammalian Development, Homeostasis, and Raf-Induced Hyperplasia

Scholl, F. A., Dumesic, P. A., Barragan, D. I., Harada, K., Bissonauth, V., Charron, J., & Khavari, P. A. (2007) · Developmental Cell · doi:10.1016/j.devcel.2007.03.009 · Cited by 142 · see citing works

Allele-Specific Mechanisms of Activation of MEK1 Mutants Determine Their Properties

Gao, Y., Chang, M. T., McKay, D., Na, N., Zhou, B., Yaeger, R. D., Torres, N. M., Muniz, K., Drosten, M., Barbacid, M., et al. (2018) · Cancer Discovery · doi:10.1158/2159-8290.cd-17-1452 · Cited by 142 · see citing works

Targeting the Raf kinases in human cancer: the Raf dimer dilemma

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Targeting RAS-mutant cancers: is ERK the key?

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Overlapping and specific functions of Braf and Craf-1 proto-oncogenes during mouse embryogenesis

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c-RAF ablation induces regression of advanced Kras/Trp53 mutant lung adenocarcinomas by a mechanism independent of MAPK signaling

Sanclemente, M., Francoz, S., Esteban-Burgos, L., Bousquet-Mur, E., Djurec, M., Lopez-Casas, P. P., Hidalgo, M., Guerra, C., Drosten, M., Musteanu, M., et al. (2018) · Cancer Cell · doi:10.1016/j.ccell.2017.12.014 · Cited by 119 · see citing works

Alike but Different: RAF Paralogs and Their Signaling Outputs

Desideri, E., Cavallo, A. L., & Baccarini, M. (2015) · Cell · doi:10.1016/j.cell.2015.04.045 · Cited by 119 · see citing works

Raf-1 Physically Interacts with Rb and Regulates Its Function: a Link between Mitogenic Signaling and Cell Cycle Regulation

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Inhibition of Ras/Raf/MEK/ERK Pathway Signaling by a Stress-Induced Phospho-Regulatory Circuit

Ritt, D. A., Abreu‐Blanco, M. T., Bindu, L. K., Durrant, D., Zhou, M., Specht, S. I., Stephen, A. G., Holderfield, M. T., & Morrison, D. K. (2016) · Molecular Cell · doi:10.1016/j.molcel.2016.10.029 · Cited by 118 · see citing works

Complete regression of advanced pancreatic ductal adenocarcinomas upon combined inhibition of EGFR and C-RAF

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Essential role of B-Raf in ERK activation during extraembryonic development

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Functional Redundancy of ERK1 and ERK2 MAP Kinases during Development

Frémin, C., Saba-El-Leil, M. K., Lévesque, K., Ang, S., & Meloche, S. (2015) · Cell Reports · doi:10.1016/j.celrep.2015.07.011 · Cited by 106 · see citing works

Loss of p53 induces cell proliferation via Ras-independent activation of the Raf/Mek/Erk signaling pathway

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Raf-1 Addiction in Ras-Induced Skin Carcinogenesis

Ehrenreiter, K., Kern, F., Velamoor, V., Meissl, K., Galabova‐Kovacs, G., Sibilia, M. C., & Baccarini, M. (2009) · Cancer Cell · doi:10.1016/j.ccr.2009.06.008 · Cited by 103 · see citing works

MEK1 Is Required for PTEN Membrane Recruitment, AKT Regulation, and the Maintenance of Peripheral Tolerance

Zmajkovicova, K., Jesenberger, V., Catalanotti, F., Baumgärtner, C., Reyes, G. X., & Baccarini, M. (2013) · Molecular Cell · doi:10.1016/j.molcel.2013.01.037 · Cited by 99 · see citing works

CRAF Autophosphorylation of Serine 621 Is Required to Prevent Its Proteasome-Mediated Degradation

Noble, C., Mercer, K., Hussain, J., Carragher, L., Giblett, S. M., Hayward, R., Patterson, C., Marais, R., & Pritchard, C. A. (2008) · Molecular Cell · doi:10.1016/j.molcel.2008.08.026 · Cited by 92 · see citing works

Heterogeneous Nuclear Ribonucleoprotein H Blocks MST2-Mediated Apoptosis in Cancer Cells by Regulating a-raf Transcription

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Raf-1 sets the threshold of Fas sensitivity by modulating Rok-α signaling

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Requirement forMap2k1(Mek1) in extra-embryonic ectoderm during placentogenesis

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