Targeting RAS–RAF–MEK–ERK signaling pathway in human cancer: Current status in clinical trials

PD-1 and PD-L1 Immune Checkpoint Blockade to Treat Breast Cancer

Hartkopf, A. D., Taran, F., Wallwiener, M., Walter, C. B., Krämer, B., Grischke, E., & Brucker, S. Y. (2016) · Breast Care · doi:10.1159/000453569 · Cited by 30,989

Adverse Renal Effects of Immune Checkpoint Inhibitors: A Narrative Review

Wanchoo, R., Karam, S., Uppal, N. N., Barta, V. S., Deray, G., Devoe, C., Launay‐Vacher, V., Jhaveri, K. D., & on behalf of Cancer and Kidney International Network Workgroup on Immune Checkpoint Inhibitors (2017) · American Journal of Nephrology · doi:10.1159/000455014 · Cited by 15,320

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

Pembrolizumab versus docetaxel for previously treated, PD-L1-positive, advanced non-small-cell lung cancer (KEYNOTE-010): a randomised controlled trial

Herbst, R. S., Baas, P., Kim, D.-W., Felip, E., Pérez-Gracia, J. L., Han, J.-Y., Molina, J., Kim, J.-H., Arvis, C. D., Ahn, M.-J., et al. (2016) · The Lancet · doi:10.1016/s0140-6736(15)01281-7 · Cited by 6,449

Mammalian MAP kinase signalling cascades

Chang, L., & Karin, M. (2001) · Nature · doi:10.1038/35065000 · Cited by 5,118

Atezolizumab versus docetaxel in patients with previously treated non-small-cell lung cancer (OAK): a phase 3, open-label, multicentre randomised controlled trial

Rittmeyer, A., Barlési, F., Waterkamp, D., Park, K., Ciardiello, F., von Pawel, J., Gadgeel, S. M., Hida, T., Kowalski, D. M., Cobo, M., et al. (2016) · The Lancet · doi:10.1016/s0140-6736(16)32517-x · Cited by 4,718

Mechanism of Activation of the RAF-ERK Signaling Pathway by Oncogenic Mutations of B-RAF

Wan, P., Garnett, M. J., Roe, S. M., Lee, S., Niculescu‐Duvaz, D., Good, V. M., Cancer Genome Project, Jones, C. M., Marshall, C. J., Springer, C. J., et al. (2004) · Cell · doi:10.1016/s0092-8674(04)00215-6 · Cited by 2,863

K-Ras(G12C) inhibitors allosterically control GTP affinity and effector interactions

Ostrem, J. M., Peters, U., Sos, M. L., Wells, J. A., & Shokat, K. M. (2013) · Nature · doi:10.1038/nature12796 · Cited by 2,557

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

Canon, J., Rex, K., Saiki, A. Y., Mohr, C., Cooke, K., Bagal, D., Gaida, K., Holt, T., Knutson, C. G., Koppada, N., et al. (2019) · Nature · doi:10.1038/s41586-019-1694-1 · Cited by 2,277

Melanomas acquire resistance to B-RAF(V600E) inhibition by RTK or N-RAS upregulation

Nazarian, R., Shi, H., Wang, Q., Kong, X., Koya, R. C., Lee, H., Chen, Z., Lee, M., Attar, N., Sazegar, H., et al. (2010) · Nature · doi:10.1038/nature09626 · Cited by 2,244

Combined Vemurafenib and Cobimetinib in BRAF -Mutated Melanoma

Larkin, J., Ascierto, P. A., Dréno, B., Atkinson, V. G., Liszkay, G., Maio, M., Mandalà, M., Демидов, Л. В., Stroyakovskiy, D., Thomas, L., et al. (2014) · New England Journal of Medicine · doi:10.1056/nejmoa1408868 · Cited by 2,115

Unresponsiveness of colon cancer to BRAF(V600E) inhibition through feedback activation of EGFR

Prahallad, A., Sun, C., Huang, S., Di Nicolantonio, F., Salazar, R., Zecchin, D., Beijersbergen, R. L., Bardelli, A., & Bernards, R. (2012) · Nature · doi:10.1038/nature10868 · Cited by 2,051

RAS Proteins and Their Regulators in Human Disease

Simanshu, D. K., Nissley, D. V., & McCormick, F. (2017) · Cell · doi:10.1016/j.cell.2017.06.009 · Cited by 1,943

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 1,841

Signaling pathway of MAPK/ERK in cell proliferation, differentiation, migration, senescence and apoptosis

Sun, Y., Liu, W., Liu, T., Xu, F., Yang, N., & Zhou, H. (2015) · Journal of Receptors and Signal Transduction · doi:10.3109/10799893.2015.1030412 · Cited by 1,833

Tumour micro-environment elicits innate resistance to RAF inhibitors through HGF secretion

Straussman, R., Morikawa, T., Shee, K., Barzily-Rokni, M., Qian, Z. R., Du, J., Davis, A., Mongare, M. M., Gould, J., Frederick, D. T., et al. (2012) · Nature · doi:10.1038/nature11183 · Cited by 1,771

Targeting PI3K in cancer: mechanisms and advances in clinical trials

Yang, J., Nie, J., Ma, X., Wei, Y., Peng, Y., & Wei, X. (2019) · Molecular Cancer · doi:10.1186/s12943-019-0954-x · Cited by 1,581

COT drives resistance to RAF inhibition through MAP kinase pathway reactivation

Johannessen, C. M., Boehm, J. S., Kim, S. Y., Thomas, S. R., Wardwell, L., Johnson, L. A., Emery, C. M., Stransky, N., Cogdill, A. P., Barretina, J., et al. (2010) · Nature · doi:10.1038/nature09627 · Cited by 1,460

RAF inhibitor resistance is mediated by dimerization of aberrantly spliced BRAF(V600E)

Poulikakos, P. I., Persaud, Y., Janakiraman, M., Kong, X., Ng, C., Moriceau, G., Shi, H., Atefi, M., Titz, B., Gabay, M. T., et al. (2011) · Nature · doi:10.1038/nature10662 · Cited by 1,454

Discovery of a selective inhibitor of oncogenic B-Raf kinase with potent antimelanoma activity

Tsai, J., Lee, J. T., Wang, W., Zhang, J., Cho, H., Mamo, S., Bremer, R., Gillette, S., Kong, J., Haass, N. K., et al. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0711741105 · Cited by 1,346

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

Acquired Resistance to BRAF Inhibitors Mediated by a RAF Kinase Switch in Melanoma Can Be Overcome by Cotargeting MEK and IGF-1R/PI3K

Villanueva, J., Vultur, A., Lee, J. T., Somasundaram, R., Fukunaga‐Kalabis, M., Cipolla, A. K., Wubbenhorst, B. S., Xu, X., Gimotty, P. A., Kee, D., et al. (2010) · Cancer Cell · doi:10.1016/j.ccr.2010.11.023 · Cited by 1,289

Regulation of the mTOR Complex 1 Pathway by Nutrients, Growth Factors, and Stress

Sengupta, S., Peterson, T. R., & Sabatini, D. M. (2010) · Molecular Cell · doi:10.1016/j.molcel.2010.09.026 · Cited by 1,275

Acquired Resistance to KRAS G12C Inhibition in Cancer

Awad, M. M., Liu, S., Rybkin, I. I., Arbour, K. C., Dilly, J., Zhu, V. W., Johnson, M. L., Heist, R. S., Patil, T., Riely, G. J., et al. (2021) · New England Journal of Medicine · doi:10.1056/nejmoa2105281 · Cited by 1,247

The MAPK signalling pathways and colorectal cancer

Fang, J. Y., & Richardson, B. C. (2005) · The Lancet Oncology · doi:10.1016/s1470-2045(05)70168-6 · Cited by 1,185

Targeting KRAS mutant cancers with a covalent G12C-specific inhibitor

Janes, M. R., Zhang, J., Li, L.-S., Hansen, R., Peters, U., Guo, X., Chen, Y., Babbar, A., Firdaus, S. J., Darjania, L., et al. (2018) · Cell · doi:10.1016/j.cell.2018.01.006 · Cited by 1,172

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

RAS Mutations in Cutaneous Squamous-Cell Carcinomas in Patients Treated with BRAF Inhibitors

Su, F., Virós, A., Milagre, C. S., Trunzer, K., Bollag, G. E., Spleiss, O., Reis-Filho, J. S., Kong, X., Koya, R. C., Flaherty, K. T., et al. (2012) · New England Journal of Medicine · doi:10.1056/nejmoa1105358 · Cited by 1,056

EGFR-Mediated Reactivation of MAPK Signaling Contributes to Insensitivity of BRAF -Mutant Colorectal Cancers to RAF Inhibition with Vemurafenib

Corcoran, R. B., Ebi, H., Turke, A. B., Coffee, E. M., Nishino, M., Cogdill, A. P., Brown, R. D., Della Pelle, P., Dias-Santagata, D., Hung, K. E., et al. (2012) · Cancer Discovery · doi:10.1158/2159-8290.cd-11-0341 · Cited by 1,022

Acquired Resistance and Clonal Evolution in Melanoma during BRAF Inhibitor Therapy

Shi, H., Hugo, W., Kong, X., Hong, A., Koya, R. C., Moriceau, G., Chodon, T., Guo, R., Johnson, D. B., Dahlman, K. B., et al. (2014) · Cancer Discovery · doi:10.1158/2159-8290.cd-13-0642 · Cited by 982

The Genetic Landscape of Clinical Resistance to RAF Inhibition in Metastatic Melanoma

Allen, E. M. V., Wagle, N., Sucker, A., Treacy, D. J., Johannessen, C. M., Goetz, E. M., Place, C. S., Taylor-Weiner, A. N., Whittaker, S. R., Kryukov, G. V., et al. (2013) · Cancer Discovery · doi:10.1158/2159-8290.cd-13-0617 · Cited by 921

The role of BRAF V600 mutation in melanoma

Ascierto, P. A., Kirkwood, J. M., Grob, J., Simeone, E., Grimaldi, A. M., Maio, M., Palmieri, G., Testori, A., Marincola, F. M., & Mozzillo, N. (2012) · Journal of Translational Medicine · doi:10.1186/1479-5876-10-85 · Cited by 849

Selective inhibition of oncogenic KRAS output with small molecules targeting the inactive state

Patricelli, M. P., Janes, M. R., Li, L.-S., Hansen, R., Peters, U., Kessler, L. V., Chen, Y., Kucharski, J. M., Feng, J., Ely, T., et al. (2016) · Cancer Discovery · doi:10.1158/2159-8290.cd-15-1105 · Cited by 759

Dual-specificity phosphatases: critical regulators with diverse cellular targets

Patterson, K. I., Brummer, T., O'brien, P. M., & Daly, R. J. (2009) · Biochemical Journal · doi:10.1042/bj20082234 · Cited by 744

MAP Kinase Inhibition Promotes T Cell and Anti-tumor Activity in Combination with PD-L1 Checkpoint Blockade.

Ebert, P. J. R., Cheung, J., Yang, Y., McNamara, E., Hong, R., Moskalenko, M., Gould, S. E., Maecker, H., Irving, B. A., Kim, J. M., et al. (2016) · Immunity · doi:10.1016/j.immuni.2016.01.024 · Cited by 713

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

Regulation of Raf-1 by direct feedback phosphorylation.

Dougherty, M., Müller, J., Ritt, D. A., Zhou, M., Zhou, X.-Z., Copeland, T., Conrads, T., Veenstra, T., Lu, K., & Morrison, D. (2005) · Molecules and Cells · doi:10.1016/j.molcel.2004.11.055 · Cited by 663

MEK1 mutations confer resistance to MEK and B-RAF inhibition

Emery, C. M., Vijayendran, K. G., Zipser, M. C., Sawyer, A. M., Niu, L., Kim, J. J., Hatton, C., Chopra, R., Oberholzer, P. A., Karpova, M. B., et al. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0905833106 · Cited by 656

Small molecules, big impact: 20 years of targeted therapy in oncology

Bedard, P. L., Hyman, D. M., Davids, M. S., & Siu, L. L. (2020) · The Lancet · doi:10.1016/s0140-6736(20)30164-1 · Cited by 637

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

Non-genomic and Immune Evolution of Melanoma Acquiring MAPKi Resistance

Hugo, W., Shi, H., Sun, L., Piva, M., Song, C., Kong, X., Moriceau, G., Hong, A., Dahlman, K. B., Johnson, D. B., et al. (2015) · Cell · doi:10.1016/j.cell.2015.07.061 · Cited by 618

GSK1120212 (JTP-74057) Is an Inhibitor of MEK Activity and Activation with Favorable Pharmacokinetic Properties for Sustained In Vivo Pathway Inhibition

Gilmartin, A. G., Bleam, M. R., Groy, A., Moss, K. G., Minthorn, E. A., Kulkarni, S. G., Rominger, C. M., Erskine, S. G., Fisher, K. E., Yang, J., et al. (2011) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-10-2200 · Cited by 590

PTEN Loss Confers BRAF Inhibitor Resistance to Melanoma Cells through the Suppression of BIM Expression

Paraiso, K. H. T., Xiang, Y., Rebecca, V. W., Abel, E. V., Chen, Y. A., Munko, A. C., Wood, E. R., Smalley, I., Sondak, V. K., Anderson, A. R. A., et al. (2011) · Cancer Research · doi:10.1158/0008-5472.can-10-2954 · Cited by 568

p70S6 kinase signals cell survival as well as growth, inactivating the pro-apoptotic molecule BAD

Harada, H., Andersen, J., Mann, M., Terada, N., & Korsmeyer, S. J. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.171301998 · Cited by 559

Drug resistance via feedback activation of Stat3 in oncogene-addicted cancer cells

Lee, H.-J., Zhuang, G., Cao, Y., Du, P., Kim, H.-J., & Settleman, J. (2014) · Cancer Cell · doi:10.1016/j.ccr.2014.05.019 · Cited by 555

The Hippo effector YAP promotes resistance to RAF- and MEK-targeted cancer therapies

Lin, L., Sabnis, A. J., Chan, E., Olivas, V., Cade, L., Pazarentzos, E., Asthana, S., Neel, D., Yan, J. J., Lu, X., et al. (2015) · Nature Genetics · doi:10.1038/ng.3218 · Cited by 551

RAS/MAPK Activation Is Associated with Reduced Tumor-Infiltrating Lymphocytes in Triple-Negative Breast Cancer: Therapeutic Cooperation Between MEK and PD-1/PD-L1 Immune Checkpoint Inhibitors

Loi, S., Dushyanthen, S., Beavis, P. A., Salgado, R., Denkert, C., Savas, P., Combs, S., Rimm, D. L., Giltnane, J. M., Estrada, M. V., et al. (2016) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-15-1125 · Cited by 536

The MAPK and AMPK signalings: interplay and implication in targeted cancer therapy

Yuan, J., Dong, X., Yap, J., & Hu, J. (2020) · Journal of Hematology & Oncology · doi:10.1186/s13045-020-00949-4 · Cited by 516

Targeting the MAPK pathway in KRAS-driven tumors

Drosten, M., & Barbacid, M. (2020) · Cancer Cell · doi:10.1016/j.ccell.2020.03.013 · Cited by 512

Binimetinib versus dacarbazine in patients with advanced NRAS-mutant melanoma (NEMO): a multicentre, open-label, randomised, phase 3 trial

Dummer, R., Schadendorf, D., Ascierto, P. A., Arance, A. M., Dutriaux, C., Giacomo, A. M. D., Rutkowski, P. L., Vecchio, M. D., Gutzmer, R., Mandalà, M., et al. (2017) · The Lancet Oncology · doi:10.1016/s1470-2045(17)30180-8 · Cited by 508

A dimerization-dependent mechanism drives RAF catalytic activation

Rajakulendran, T., Sahmi, M., Lefrançois, M., Sicheri, F., & Therrien, M. (2009) · Nature · doi:10.1038/nature08314 · Cited by 505

Tumour cell survival signalling by the ERK1/2 pathway

Balmanno, K., & Cook, S. J. (2009) · Cell Death & Differentiation · doi:10.1038/cdd.2008.148 · Cited by 484

MAP Kinase Pathway Alterations in BRAF -Mutant Melanoma Patients with Acquired Resistance to Combined RAF/MEK Inhibition

Wagle, N., Van Allen, E. M., Treacy, D. J., Frederick, D. T., Cooper, Z. A., Taylor-Weiner, A., Rosenberg, M., Goetz, E. M., Sullivan, R. J., Farlow, D. N., et al. (2014) · Cancer Discovery · doi:10.1158/2159-8290.cd-13-0631 · Cited by 478

Targeting ER stress–induced autophagy overcomes BRAF inhibitor resistance in melanoma

Ma, X.-H., Piao, S.-F., Dey, S., Mcafee, Q., Karakousis, G., Villanueva, J., Hart, L. S., Levi, S., Hu, J., Zhang, G., et al. (2014) · Journal of Clinical Investigation · doi:10.1172/jci70454 · Cited by 457

Targeting ERK, an Achilles' Heel of the MAPK pathway, in cancer therapy

Liu, F., Yang, X., Geng, M., & Huang, M. (2018) · Acta Pharmaceutica Sinica B · doi:10.1016/j.apsb.2018.01.008 · Cited by 451

MED12 Controls the Response to Multiple Cancer Drugs through Regulation of TGF-β Receptor Signaling

Huang, S., Hölzel, M., Knijnenburg, T., Schlicker, A., Roepman, P., McDermott, U., Garnett, M., Grernrum, W., Sun, C., Prahallad, A., et al. (2012) · Cell · doi:10.1016/j.cell.2012.10.035 · Cited by 430

Wild-Type and Mutant B-RAF Activate C-RAF through Distinct Mechanisms Involving Heterodimerization

Garnett, M. J., Rana, S., Paterson, H., Barford, D., & Marais, R. (2005) · Molecular Cell · doi:10.1016/j.molcel.2005.10.022 · Cited by 416

The clinical development of MEK inhibitors

Zhao, Y., & Adjei, A. A. (2014) · Nature Reviews Clinical Oncology · doi:10.1038/nrclinonc.2014.83 · Cited by 410

A combinatorial strategy for treating KRAS-mutant lung cancer

Manchado, E., Weissmueller, S., Morris, J. P., Chen, C.-C., Wullenkord, R., Lujambio, A., de Stanchina, E., Poirier, J. T., Gainor, J. F., Corcoran, R. B., et al. (2016) · Nature · doi:10.1038/nature18600 · Cited by 403

Resistance to BRAF-targeted therapy in melanoma

Sullivan, R. J., & Flaherty, K. T. (2013) · European Journal of Cancer · doi:10.1016/j.ejca.2012.11.019 · Cited by 386

Relief of Feedback Inhibition of HER3 Transcription by RAF and MEK Inhibitors Attenuates Their Antitumor Effects in BRAF -Mutant Thyroid Carcinomas

Montero-Conde, C., Ruiz-Llorente, S., Dominguez, J. M., Knauf, J. A., Viale, A., Sherman, E. J., Ryder, M., Ghossein, R. A., Rosen, N., & Fagin, J. A. (2013) · Cancer Discovery · doi:10.1158/2159-8290.cd-12-0531 · Cited by 382

Increased MAPK reactivation in early resistance to dabrafenib/trametinib combination therapy of BRAF-mutant metastatic melanoma

Long, G. V., Fung, C., Menzies, A. M., Pupo, G. M., Carlino, M. S., Hyman, J., Shahheydari, H., Tembe, V., Thompson, J. F., Saw, R. P., et al. (2014) · Nature Communications · doi:10.1038/ncomms6694 · Cited by 375

A molecular assembly phase transition and kinetic proofreading modulate Ras activation by SOS

Huang, W. Y. C., Alvarez, S. A., Kondo, Y., Lee, Y. K., Chung, J. K., Lam, H. Y. M., Biswas, K. H., Kuriyan, J., & Groves, J. T. (2019) · Science · doi:10.1126/science.aau5721 · Cited by 352

Tunable-Combinatorial Mechanisms of Acquired Resistance Limit the Efficacy of BRAF/MEK Cotargeting but Result in Melanoma Drug Addiction

Moriceau, G., Hugo, W., Hong, A., Shi, H., Kong, X., Yu, C. C., Koya, R. C., Samatar, A. A., Khanlou, N., Braun, J. G., et al. (2015) · Cancer Cell · doi:10.1016/j.ccell.2014.11.018 · Cited by 351

BRAF Gene Amplification Can Promote Acquired Resistance to MEK Inhibitors in Cancer Cells Harboring the BRAF V600E Mutation

Corcoran, R. B., Dias-Santagata, D., Bergethon, K., Iafrate, A. J., Settleman, J., & Engelman, J. A. (2010) · Science Signaling · doi:10.1126/scisignal.2001148 · Cited by 350

Effects of MAPK and PI3K Pathways on PD-L1 Expression in Melanoma

Atefi, M. S., Avramis, E. V., Lassen, A., Wong, D. J. L., Robert, L., Foulad, D. S., Cerniglia, M., Titz, B., Chodon, T., Graeber, T. G., et al. (2014) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-13-2797 · Cited by 344

Myeloid cells are required for PD-1/PD-L1 checkpoint activation and the establishment of an immunosuppressive environment in pancreatic cancer

Zhang, Y., Velez-Delgado, A., Mathew, E., Li, D., Mendez, F., Flannagan, K., Rhim, A. D., Simeone, D. M., Beatty, G. L., & di Magliano, M. P. (2016) · Gut · doi:10.1136/gutjnl-2016-312078 · Cited by 339

Acquired BRAF inhibitor resistance: A multicenter meta-analysis of the spectrum and frequencies, clinical behaviour, and phenotypic associations of resistance mechanisms

Johnson, D. B., Menzies, A. M., Zimmer, L., Eroglu, Z., Ye, F., Zhao, S., Rizos, H., Sucker, A., Scolyer, R. A., Gutzmer, R., et al. (2015) · European Journal of Cancer · doi:10.1016/j.ejca.2015.08.022 · Cited by 331

Increased cyclin D1 expression can mediate BRAF inhibitor resistance in BRAF V600E–mutated melanomas

Smalley, K. S. M., Lioni, M., Palma, M. D., Xiao, M., Desai, B. M., Egyházi, S., Hansson, J., Wu, H., King, A. J., Belle, P. A. V., et al. (2008) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-08-0431 · Cited by 328

Mechanism of MEK inhibition determines efficacy in mutant KRAS- versus BRAF-driven cancers

Hatzivassiliou, G., Haling, J. R., Chen, H., Song, K. W., Price, S., Heald, R. A., Hewitt, J. F. M., Zak, M., Peck, A., Orr, C., et al. (2013) · Nature · doi:10.1038/nature12441 · Cited by 317

SHP2 inhibition prevents adaptive resistance to MEK inhibitors in multiple cancer models

Fedele, C., Ran, H., Diskin, B., Wei, W., Jen, J., Geer, M. J., Araki, K., Ozerdem, U., Simeone, D. M., Miller, G., et al. (2018) · Cancer Discovery · doi:10.1158/2159-8290.cd-18-0444 · Cited by 315

Targeting ERK1/2 protein-serine/threonine kinases in human cancers

Roskoski, R. J. (2019) · Pharmacological Research · doi:10.1016/j.phrs.2019.01.039 · Cited by 314

Active Ras induces heterodimerization of cRaf and BRaf.

Weber, C., Slupsky, J. R., Kalmes, H. A., & Rapp, U. R. (2001) · PubMed · Cited by 312

Intrinsic resistance to MEK inhibition in KRAS mutant lung and colon cancer through transcriptional induction of ERBB3

Sun, C., Hobor, S., Bertotti, A., Zecchin, D., Huang, S., Galimi, F., Cottino, F., Prahallad, A., Grernrum, W., Tzani, A., et al. (2014) · Cell Reports · doi:10.1016/j.celrep.2014.02.045 · Cited by 304

Allosteric Activation of Functionally Asymmetric RAF Kinase Dimers

Hu, J., Stites, E. C., Yu, H., Germino, E., Meharena, H. S., Stork, P. A., Kornev, A. P., Taylor, S. S., & Shaw, A. S. (2013) · Cell · doi:10.1016/j.cell.2013.07.046 · Cited by 303

Combination of vemurafenib and cobimetinib in patients with advanced BRAFV600-mutated melanoma: a phase 1b study

Ribas, A., Gonzalez, R. C., Pavlick, A. C., Hamid, O., Gajewski, T. F., DAUD, A. I., Flaherty, L. E., Logan, T. F., Chmielowski, B., Lewis, K. D., et al. (2014) · The Lancet Oncology · doi:10.1016/s1470-2045(14)70301-8 · Cited by 303

Dusp6 (Mkp3) is a negative feedback regulator of FGF-stimulated ERK signaling during mouse development

Li, C., Scott, D., Hatch, E., Tian, X.-Y., & Mansour, S. (2007) · Development · doi:10.1242/dev.02701 · Cited by 298

MEK inhibitors for the treatment of non-small cell lung cancer

Han, J., Liu, Y., Yang, S., Wu, X., Li, H., & Wang, Q. (2021) · Journal of Hematology & Oncology · doi:10.1186/s13045-020-01025-7 · Cited by 293

Over-expression of the mitogen-activated protein kinase (MAPK) kinase (MEK)-MAPK in hepatocellular carcinoma: Its role in tumor progression and apoptosis

Huynh, H. T., Nguyen, T. T. T., Chow, P. K. H., Tan, P. H., Soo, K. C., & Tran, E. (2003) · BMC Gastroenterology · doi:10.1186/1471-230x-3-19 · Cited by 289

Mechanisms of resistance to BRAF and MEK inhibitors and clinical update of US Food and Drug Administration-approved targeted therapy in advanced melanoma

Kakadia, S., Yarlagadda, N., Awad, R., Kundranda, M., Niu, J., Naraev, B., Mina, L., Dragovich, T., Gimbel, M., & Mahmoud, F. (2018) · OncoTargets and Therapy · doi:10.2147/ott.s182721 · Cited by 277

Inhibition of autophagy potentiates the antitumor effect of the multikinase inhibitor sorafenib in hepatocellular carcinoma

Shimizu, S., Takehara, T., Hikita, H., Kodama, T., Tsunematsu, H., Miyagi, T., Hosui, A., Ishida, H., Tatsumi, T., Kanto, T., et al. (2011) · International Journal of Cancer · doi:10.1002/ijc.26374 · Cited by 269

Mutant BRAF Melanomas—Dependence and Resistance

Poulikakos, P. I., & Rosen, N. X. (2011) · Cancer Cell · doi:10.1016/j.ccr.2011.01.008 · Cited by 256

Impact of Feedback Phosphorylation and Raf Heterodimerization on Normal and Mutant B-Raf Signaling

Ritt, D. A., Monson, D. M., Specht, S. I., & Morrison, D. K. (2009) · Molecular and Cellular Biology · doi:10.1128/mcb.00569-09 · Cited by 239

Interplay between MAPK/ERK signaling pathway and MicroRNAs: A crucial mechanism regulating cancer cell metabolism and tumor progression

Asl, E. R., Amini, M. A., Najafi, S., Mansoori, B., Mokhtarzadeh, A., Mohammadi, A., Lotfinejad, P., Bagheri, M., Shirjang, S., Lotfi, Z., et al. (2021) · Life Sciences · doi:10.1016/j.lfs.2021.119499 · Cited by 236

Nuclear ERK: Mechanism of Translocation, Substrates, and Role in Cancer

Maik-Rachline, G., Hacohen-Lev-Ran, A., & Seger, R. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20051194 · Cited by 226

Effects of Raf Dimerization and Its Inhibition on Normal and Disease-Associated Raf Signaling

Freeman, A. K., Ritt, D. A., & Morrison, D. K. (2013) · Molecular Cell · doi:10.1016/j.molcel.2012.12.018 · Cited by 211

Targeting oncogenic Raf protein-serine/threonine kinases in human cancers

Roskoski, R. J. (2018) · Pharmacological Research · doi:10.1016/j.phrs.2018.08.013 · Cited by 199

BRAF Inhibitors: Molecular Targeting and Immunomodulatory Actions

Proietti, I., Skroza, N., Michelini, S., Mambrin, A., Balduzzi, V., Bernardini, N., Marchesiello, A., Tolino, E., Volpe, S., Maddalena, P., et al. (2020) · Cancers · doi:10.3390/cancers12071823 · Cited by 192

Development of encorafenib for BRAF-mutated advanced melanoma

Koelblinger, P., Olaf, T., & Dummer, R. (2017) · Current Opinion in Oncology · doi:10.1097/cco.0000000000000426 · Cited by 191

MEK inhibition reprograms CD8+ T lymphocytes into memory stem cells with potent antitumor effects

Verma, V., Jafarzadeh, N., Boi, S. K., Kundu, S., Jiang, Z., Fan, Y., Lopez, J., Nandre, R. M., Zeng, P., Alolaqi, F., et al. (2020) · Nature Immunology · doi:10.1038/s41590-020-00818-9 · Cited by 186

RAS-mediated oncogenic signaling pathways in human malignancies

Khan, A. Q., Kuttikrishnan, S., Siveen, K. S., Prabhu, K. S., Shanmugakonar, M., Al‐Naemi, H. A., Haris, M., Dermime, S., & Shahab Uddin, M. S. (2018) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2018.03.001 · Cited by 185

WNT5A enhances resistance of melanoma cells to targeted BRAF inhibitors

Anastas, J. N., Kulikauskas, R. M., Tamir, T. Y., Rizos, H., Long, G. V., von Euw, E. M., Yang, P., Chen, H., Haydu, L. E., Toroni, R. A., et al. (2014) · Journal of Clinical Investigation · doi:10.1172/jci70156 · Cited by 184

Inhibitors that stabilize a closed RAF kinase domain conformation induce dimerization

Lavoie, H., Thevakumaran, N., Gavory, G., Li, J. J., Padeganeh, A., Guiral, S., Duchaine, J., Mao, D. Y. L., Bouvier, M., Sicheri, F., et al. (2013) · Nature Chemical Biology · doi:10.1038/nchembio.1257 · Cited by 181

Identification of the Mitogen-Activated Protein Kinase Phosphorylation Sites on Human Sosl That Regulate Interaction with Grb2

Corbalán‐García, S., Yang, S., Degenhardt, K., & Bar‐Sagi, D. (1996) · Molecular and Cellular Biology · doi:10.1128/mcb.16.10.5674 · Cited by 181

Therapeutic resistance resulting from mutations in Raf/MEK/ERK and PI3K/PTEN/Akt/mTOR signaling pathways

McCubrey, J. A., Steelman, L. S., Kempf, C., Chappell, W. H., Abrams, S. L., Stivala, F., Malaponte, G., Nicoletti, F., Libra, M., Bäsecke, J., et al. (2011) · Journal of Cellular Physiology · doi:10.1002/jcp.22647 · Cited by 177

Expression of Endogenous Oncogenic V600EB-raf Induces Proliferation and Developmental Defects in Mice and Transformation of Primary Fibroblasts

Mercer, K., Giblett, S. M., Green, S. A., Lloyd, D. J., Dias, S. D. R., Plumb, M., Marais, R., & Pritchard, C. A. (2005) · Cancer Research · doi:10.1158/0008-5472.can-05-2211 · Cited by 176

Autophagy inhibition overcomes multiple mechanisms of resistance to BRAF inhibition in brain tumors

Mulcahy Levy, J. M., Zahedi, S., Griesinger, A. M., Morin, A., Davies, K. D., Aisner, D. L., Kleinschmidt-DeMasters, B., Fitzwalter, B. E., Goodall, M. L., Thorburn, J., et al. (2017) · eLife · doi:10.7554/elife.19671 · Cited by 175

Phase Ib study of atezolizumab combined with cobimetinib in patients with solid tumors.

Hellmann, M. D., Kim, T.-W., Lee, C. B., Goh, B.-C., Miller, W. H., Oh, D.-Y., Jamal, R., Chee, C.-E., Chow, L. Q. M., Gainor, J. F., et al. (2019) · Annals of Oncology · doi:10.1093/annonc/mdz113 · Cited by 174

PLX4032, a potent inhibitor of the B‐Raf V600E oncogene, selectively inhibits V600E‐positive melanomas

Lee, J. T., Li, L., Brafford, P. A., van den Eijnden, M., Halloran, M. B., Sproesser, K., Haass, N. K., Smalley, K. S. M., Tsai, J. Y., Bollag, G. E., et al. (2010) · Pigment Cell & Melanoma Research · doi:10.1111/j.1755-148x.2010.00763.x · Cited by 165

Discovery of (S)-1-(1-(4-Chloro-3-fluorophenyl)-2-hydroxyethyl)-4-(2-((1-methyl-1H-pyrazol-5-yl)amino)pyrimidin-4-yl)pyridin-2(1H)-one (GDC-0994), an Extracellular Signal-Regulated Kinase 1/2 (ERK1/2) Inhibitor in Early Clinical Development

Blake, J. F., Burkard, M., Chan, J., Chen, H., Chou, K.-J., Diaz, D., Dudley, D. A., Gaudino, J. J., Gould, S. E., Grina, J. A., et al. (2016) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.6b00389 · Cited by 159

First-in-Human Clinical Trial of Oral ONC201 in Patients with Refractory Solid Tumors

Stein, M. N., Bertino, J. R., Kaufman, H. L., Mayer, T. M., Moss, R. A., Silk, A. W., Chan, N., Malhotra, J. D., Rodriguez, L., Aisner, J., et al. (2017) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-16-2658 · Cited by 159

Targeting the MAPK and PI3K pathways in combination with PD1 blockade in melanoma

Deken, M. A., Gadiot, J., Jordanova, E. S., Lacroix, R., van Gool, M. M. J., Kroon, P., Pineda, C., Foppen, M. H. G., Scolyer, R. A., Song, J., et al. (2016) · OncoImmunology · doi:10.1080/2162402x.2016.1238557 · Cited by 155

MEK drives BRAF activation through allosteric control of KSR proteins

Lavoie, H., Sahmi, M., Maisonneuve, P., Marullo, S. A., Thevakumaran, N., Jin, T., Kurinov, I. V., Sicheri, F., & Therrien, M. (2018) · Nature · doi:10.1038/nature25478 · Cited by 152

Development of MK-8353, an orally administered ERK1/2 inhibitor, in patients with advanced solid tumors

Moschos, S. J., Sullivan, R. J., Hwu, W., Ramanathan, R. K., Adjei, A. A., Fong, P. C. C., Shapira‐Frommer, R., Tawbi, H. A.-H., Rubino, J., Rush, T. S., et al. (2018) · JCI Insight · doi:10.1172/jci.insight.92352 · Cited by 151

Encorafenib and Binimetinib: First Global Approvals

Shirley, M. (2018) · Drugs · doi:10.1007/s40265-018-0963-x · Cited by 149

Ras activation revisited: role of GEF and GAP systems

Hennig, A., Markwart, R., Esparza-Franco, M. A., Ladds, G., & Rubio, I. (2015) · Biological Chemistry · doi:10.1515/hsz-2014-0257 · Cited by 146

Targeted Therapy in Advanced Thyroid Cancer to Resensitize Tumors to Radioactive Iodine

Jaber, T., Waguespack, S. G., Cabanillas, M. E., Elbanan, M., Vu, T. H., Dadu, R., Sherman, S. I., Amit, M., Santos, E. B., Zafereo, M., et al. (2018) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2018-00612 · Cited by 142

Phase II Trial of MEK Inhibitor Selumetinib (AZD6244, ARRY-142886) in Patients with BRAFV600E/K-Mutated Melanoma

Catalanotti, F., Solit, D. B., Pulitzer, M. P., Berger, M. F., Scott, S. N., Iyriboz, T. A., Lacouture, M. E., Panageas, K. S., Wolchok, J. D., Carvajal, R. D., et al. (2013) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-12-3476 · Cited by 135

Radiosensitization by BRAF inhibitor therapy—mechanism and frequency of toxicity in melanoma patients

Hecht, M., Zimmer, L., Loquai, C., Weishaupt, C., Gutzmer, R., Schuster, B., Gleisner, S., Schulze, B., Goldinger, S. M., Berking, C., et al. (2015) · Annals of Oncology · doi:10.1093/annonc/mdv139 · Cited by 132

ERK-Dependent MKP-1–Mediated Cisplatin Resistance in Human Ovarian Cancer Cells

Wang, J., Zhou, J., & Wu, G. S. (2007) · Cancer Research · doi:10.1158/0008-5472.can-07-5185 · Cited by 129

Oncogenic PI3K/AKT promotes the step-wise evolution of combination BRAF/MEK inhibitor resistance in melanoma

Irvine, M., Stewart, A., Pedersen, B., Boyd, S. C., Kefford, R. F., & Rizos, H. (2018) · Oncogenesis · doi:10.1038/s41389-018-0081-3 · Cited by 120

Identification of novel ERK-mediated feedback phosphorylation sites at the C-terminus of B-Raf

Brummer, T., Naegele, H., Reth, M. G., & Misawa, Y. (2003) · Oncogene · doi:10.1038/sj.onc.1207185 · Cited by 115

Selumetinib: First Approval

Markham, A., & Keam, S. J. (2020) · Drugs · doi:10.1007/s40265-020-01331-x · Cited by 112

Mapping the molecular determinants of BRAF oncogene dependence in human lung cancer

Lin, L., Asthana, S., Chan, E., Bandyopadhyay, S., Martins, M. M., Olivas, V. R., Yan, J. J., Pham, L. Q., Wang, M. M., Bollag, G. E., et al. (2014) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1320956111 · Cited by 104

Increased MAPK Activity and MKP-1 Overexpression in Human Gastric Adenocarcinoma

Bang, Y., Kwon, J. H., Kang, S. H., Kim, J. W., & Yang, Y. C. (1998) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.1998.9256 · Cited by 104

Grb2, a Double-Edged Sword of Receptor Tyrosine Kinase Signaling

Belov, A. A., & Mohammadi, M. (2012) · Science Signaling · doi:10.1126/scisignal.2003576 · Cited by 103

Integrin α6/Akt/Erk signaling is essential for human breast cancer resistance to radiotherapy

Hu, T., Zhou, R., Zhao, Y., & Wu, G. (2016) · Scientific Reports · doi:10.1038/srep33376 · Cited by 96

PD-L1 Expression and Immune Escape in Melanoma Resistance to MAPK Inhibitors

Kakavand, H., Rawson, R. V., Pupo, G. M., Yang, J. Y. H., Menzies, A. M., Carlino, M. S., Kefford, R. F., Howle, J. R., Saw, R. P. M., Thompson, J. F., et al. (2017) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-16-1688 · Cited by 96

Immunotherapy Combined or Sequenced With Targeted Therapy in the Treatment of Solid Tumors: Current Perspectives

Atkins, M. B., & Larkin, J. (2016) · JNCI Journal of the National Cancer Institute · doi:10.1093/jnci/djv414 · Cited by 92

PD-L1 blockade in combination with inhibition of MAPK oncogenic signaling in patients with advanced melanoma

Ribas, A., Algazi, A. P., Ascierto, P. A., Butler, M. O., Chandra, S., Gordon, M. S., Hernandez-Aya, L. F., Lawrence, D. P., Lutzky, J., Miller, W. H., et al. (2020) · Nature Communications · doi:10.1038/s41467-020-19810-w · Cited by 92

RSK phosphorylates SOS1 creating 14-3-3-docking sites and negatively regulating MAPK activation

Saha, M., Carriere, A., Cheerathodi, M., Zhang, X., Lavoie, G., Rush, A. J., Roux, P. P., & Ballif, B. A. (2012) · Biochemical Journal · doi:10.1042/bj20120938 · Cited by 88

Loss of cohesin complex components STAG2 or STAG3 confers resistance to BRAF inhibition in melanoma

Shen, C., Kim, S. H., Trousil, S., Frederick, D. T., Piris, A., Yuan, P., Cai, L., Gu, L., Li, M., Lee, J. H., et al. (2016) · Nature Medicine · doi:10.1038/nm.4155 · Cited by 86

A First-in-Human Phase I Study to Evaluate the ERK1/2 Inhibitor GDC-0994 in Patients with Advanced Solid Tumors

Varga, A., Soria, J., Hollebecque, A., LoRusso, P. M., Bendell, J. C., Huang, S.-M. A., Wagle, M.-C., Okrah, K., Liu, L., Murray, E. R., et al. (2019) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-19-2574 · Cited by 85

Targeting Mitochondrial Metabolism by Inhibiting Autophagy in BRAF-Driven Cancers

Strohecker, A. M., & White, E. (2014) · Cancer Discovery · doi:10.1158/2159-8290.cd-14-0196 · Cited by 83

A Landscape of Therapeutic Cooperativity in KRAS Mutant Cancers Reveals Principles for Controlling Tumor Evolution

Anderson, G. R., Winter, P. S., Lin, K. H., Nussbaum, D. P., Cakir, M., Stein, E. M., Soderquist, R. S., Crawford, L., Leeds, J. C., Newcomb, R., et al. (2017) · Cell Reports · doi:10.1016/j.celrep.2017.07.006 · Cited by 80

Oncogenic KRAS blockade therapy: renewed enthusiasm and persistent challenges

Tang, D., Kroemer, G., & Kang, R. (2021) · Molecular Cancer · doi:10.1186/s12943-021-01422-7 · Cited by 80

Identification of the MEK1(F129L) Activating Mutation as a Potential Mechanism of Acquired Resistance to MEK Inhibition in Human Cancers Carrying the B-Raf V600E Mutation

Wang, H., Daouti, S., Li, W., Yang, W., Rizzo, C., Higgins, B., Packman, K. E., Rosen, N. X., Boylan, J. F., Heimbrook, D. C., et al. (2011) · Cancer Research · doi:10.1158/0008-5472.can-10-4351 · Cited by 76

The MEK inhibitor selumetinib complements CTLA-4 blockade by reprogramming the tumor immune microenvironment

Poon, E., Mullins, S., Watkins, A., Williams, G. S., Koopmann, J., Genova, G. D., Cumberbatch, M., Veldman-Jones, M. H., Grosskurth, S. E., Sah, V. R., et al. (2017) · Journal for ImmunoTherapy of Cancer · doi:10.1186/s40425-017-0268-8 · Cited by 76

MEK inhibition may increase survival of NRAS-mutated melanoma patients treated with checkpoint blockade: Results of a retrospective multicentre analysis of 364 patients

Kirchberger, M. C., Ugurel, S., Mangana, J., Heppt, M. V., Eigentler, T., Berking, C., Schadendorf, D., Schuler, G., Dummer, R., & Heinzerling, L. (2018) · European Journal of Cancer · doi:10.1016/j.ejca.2018.04.010 · Cited by 76

Overcoming Resistance to Dual Innate Immune and MEK Inhibition Downstream of KRAS

Kitajima, S., Asahina, H., Chen, T., Guo, S., Quiceno, L. G., Cavanaugh, J. D., Merlino, A. A., Tange, S., Terai, H., Kim, J. W., et al. (2018) · Cancer Cell · doi:10.1016/j.ccell.2018.08.009 · Cited by 75

Biological Rationale for Targeting MEK/ERK Pathways in Anti-Cancer Therapy and to Potentiate Tumour Responses to Radiation

Marampon, F., Ciccarelli, C., & ZANI, B. M. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20102530 · Cited by 74

Serious Skin Toxicity With the Combination of BRAF Inhibitors and Radiotherapy

Satzger, I., Degen, A., Asper, H., Kapp, A., Hauschild, A., & Gutzmer, R. (2013) · Journal of Clinical Oncology · doi:10.1200/jco.2012.44.4265 · Cited by 74

Pulsatile MEK inhibition improves anti-tumor immunity and T cell function in murine Kras mutant lung cancer

Choi, H., Deng, J., Li, S., Silk, T., Dong, L., Brea, E. J., Houghton, S., Redmond, D., Zhong, H., Boiarsky, J., et al. (2019) · Cell Reports · doi:10.1016/j.celrep.2019.03.066 · Cited by 72

Targeting Autophagy Sensitizes BRAF-Mutant Thyroid Cancer to Vemurafenib

Wang, W., Kang, H. H., Zhao, Y., Min, I. M., Wyrwas, B., Moore, M. D., Teng, L., Zarnegar, R., Jiang, X., & Fahey, T. J. (2016) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2016-1999 · Cited by 71

PTEN Loss-of-Function Alterations Are Associated With Intrinsic Resistance to BRAF Inhibitors in Metastatic Melanoma

Catalanotti, F., Cheng, D. T., Shoushtari, A. N., Johnson, D. B., Panageas, K. S., Momtaz, P., Higham, C., Won, H. H., Harding, J. J., Merghoub, T., et al. (2017) · JCO Precision Oncology · doi:10.1200/po.16.00054 · Cited by 70

Immune checkpoint blockade and its combination therapy with small-molecule inhibitors for cancer treatment

Wang, M., Liu, Y., Cheng, Y., Wei, Y., & Wei, X. (2019) · Biochimica et Biophysica Acta (BBA) - Reviews on Cancer · doi:10.1016/j.bbcan.2018.12.002 · Cited by 66

Dynamic Modeling and Analysis of the Cross-Talk between Insulin/AKT and MAPK/ERK Signaling Pathways

Arkun, Y. (2016) · PLoS ONE · doi:10.1371/journal.pone.0149684 · Cited by 64

Role of protein phosphatases in the cancer microenvironment

Ruvolo, P. P. (2018) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2018.07.006 · Cited by 64

Activating mutations in MEK1 enhance homodimerization and promote tumorigenesis

Yuan, J., Ng, W. H., Tian, Z., Yap, J., Baccarini, M., Chen, Z., & Hu, J. (2018) · Science Signaling · doi:10.1126/scisignal.aar6795 · Cited by 63

Identification of Major ERK-Related Phosphorylation Sites in Gab1

Lehr, S., Kotzka, J., Avci, H., Sickmann, A., Meyer, H. E., Herkner, A., & Müller‐Wieland, D. (2004) · Biochemistry · doi:10.1021/bi049753e · Cited by 61

SHOC2 and CRAF Mediate ERK1/2 Reactivation in Mutant NRAS-mediated Resistance to RAF Inhibitor

Kaplan, F. M., Kugel, C. H., Dadpey, N., Shao, Y., Abel, E. V., & Aplin, A. E. (2012) · Journal of Biological Chemistry · doi:10.1074/jbc.m112.390906 · Cited by 60

Inhibiting BRAF Oncogene–Mediated Radioresistance Effectively Radiosensitizes BRAFV600E-Mutant Thyroid Cancer Cells by Constraining DNA Double-Strand Break Repair

Robb, R. N., Yang, L., Shen, C., Wolfe, A. R., Webb, A., Zhang, X., Vedaie, M., Saji, M., Jhiang, S. M., Ringel, M. D., et al. (2019) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-18-3625 · Cited by 60

Clinical responses to ERK inhibition in BRAF V600E-mutant colorectal cancer predicted using a computational model

Kirouac, D. C., Schaefer, G., Chan, J., Merchant, M., Orr, C., Huang, S.-M. A., Moffat, J., Liu, L., Gadkar, K., & Ramanujan, S. (2017) · npj Systems Biology and Applications · doi:10.1038/s41540-017-0016-1 · Cited by 60

Ulixertinib (BVD-523) antagonizes ABCB1- and ABCG2-mediated chemotherapeutic drug resistance

Ji, N., Yang, Y., Lei, Z., Cai, C., Wang, J., Gupta, P., Xian, X., Yang, D., Kong, D., & Chen, Z. (2018) · Biochemical Pharmacology · doi:10.1016/j.bcp.2018.10.028 · Cited by 60

A Phase Ib Study to Evaluate the MEK Inhibitor Cobimetinib in Combination with the ERK1/2 Inhibitor GDC-0994 in Patients with Advanced Solid Tumors

Weekes, C. D., Lockhart, A. C., LoRusso, P. M., Murray, E. R., Park, E., Tagen, M., Singh, J., Sarkar, I., Müeller, L., Dokainish, H., et al. (2020) · The Oncologist · doi:10.1634/theoncologist.2020-0292 · Cited by 58

The dimer-dependent catalytic activity of RAF family kinases is revealed through characterizing their oncogenic mutants

Yuan, J., Ng, W. H., Lam, P. Y. P., Wang, Y., Xia, H., Yap, J., Guan, S. P., Lee, A. S. G., Wang, M., Baccarini, M., et al. (2018) · Oncogene · doi:10.1038/s41388-018-0365-2 · Cited by 57

BRAF Splice Variant Resistance to RAF Inhibitor Requires Enhanced MEK Association

Vido, M. J., Le, K., Hartsough, E. J., & Aplin, A. E. (2018) · Cell Reports · doi:10.1016/j.celrep.2018.10.049 · Cited by 55

Concurrent MEK and autophagy inhibition is required to restore cell death associated danger-signalling in Vemurafenib-resistant melanoma cells

Martin, S., Dudek-Perić, A. M., Maes, H., Garg, A. D., Gabrysiak, M., Demirsoy, S., Swinnen, J. V., & Agostinis, P. (2015) · Biochemical Pharmacology · doi:10.1016/j.bcp.2014.12.003 · Cited by 54

FDA Approves First KRAS Inhibitor: Sotorasib

(2021) · Cancer Discovery · doi:10.1158/2159-8290.cd-nb2021-0362 · Cited by 54

MK-8353: Discovery of an Orally Bioavailable Dual Mechanism ERK Inhibitor for Oncology

Boga, S. B., Deng, Y., Zhu, L. W., Yang, N., Cooper, A. B., Shipps, G. W., Doll, R. J., Shih, N., Zhu, H. Y. H., Sun, R., et al. (2018) · ACS Medicinal Chemistry Letters · doi:10.1021/acsmedchemlett.8b00220 · Cited by 53

MEK inhibitors for the treatment of NRAS mutant melanoma

Sarkisian, S., & Davar, D. (2018) · Drug Design Development and Therapy · doi:10.2147/dddt.s131721 · Cited by 52

ERK Regulates HIF1α-Mediated Platinum Resistance by Directly Targeting PHD2 in Ovarian Cancer

Li, Z., Zhou, W., Zhang, Y., Sun, W., Yung, M. M. H., Sun, J. F., Li, J., Chen, C., Li, Z., Meng, Y., et al. (2019) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-18-4145 · Cited by 52

Sorafenib does not improve efficacy of chemotherapy in advanced pancreatic cancer: A GISCAD randomized phase II study

Cascinu, S., Berardi, R., Sobrero, A. F., Bidoli, P., Labianca, R., Siena, S., Ferrari, D., Barni, S., Aitini, E., Zagonel, V., et al. (2013) · Digestive and Liver Disease · doi:10.1016/j.dld.2013.09.020 · Cited by 51

MEK Inhibition Overcomes Cisplatin Resistance Conferred by SOS/MAPK Pathway Activation in Squamous Cell Carcinoma

Kong, L. R., Chua, K. N., Sim, W. J., Ng, H. C., Bi, C., Ho, J., Nga, M. E., Pang, Y. H., Ong, W. R., Soo, R. A., et al. (2015) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-15-0062 · Cited by 50

BRAF mutation and its inhibitors in sarcoma treatment

Liu, H., Nahar, N., Hassan, S., Liu, X., & Yang, J. (2020) · Cancer Medicine · doi:10.1002/cam4.3103 · Cited by 50

Kinase-independent role for CRAF-driving tumour radioresistance via CHK2

Advani, S. J., Camargo, M. F., Seguin, L., Mielgo, A., Anand, S., Hicks, A. M., Aguilera, J. A., Franovic, A., Weis, S. M., & Cheresh, D. A. (2015) · Nature Communications · doi:10.1038/ncomms9154 · Cited by 47

Astaxanthin increases radiosensitivity in esophageal squamous cell carcinoma through inducing apoptosis and G2/M arrest

Qian, X., Tan, C., Yang, B., Wang, F., Ge, Y., Guan, Z., & Cai, J. (2017) · Diseases of the Esophagus · doi:10.1093/dote/dox027 · Cited by 47

Safety and efficacy of the BRAF inhibitor dabrafenib in relapsed or refractory hairy cell leukemia: a pilot phase-2 clinical trial

Tiacci, E., Carolis, L. D., Simonetti, E., Merluzzi, M., Bennati, A., Perriello, V. M., Pucciarini, A., Santi, A., Venanzi, A., Pettirossi, V., et al. (2021) · Leukemia · doi:10.1038/s41375-021-01210-8 · Cited by 47

Inhibition of the CRAF/prohibitin interaction reverses CRAF-dependent resistance to vemurafenib

Doudican, N. A., & Orlow, S. J. (2016) · Oncogene · doi:10.1038/onc.2016.214 · Cited by 45

The Biology and Clinical Development of MEK Inhibitors for Cancer

Luke, J. J., Ott, P. A., & Shapiro, G. I. (2014) · Drugs · doi:10.1007/s40265-014-0315-4 · Cited by 42

Loss of BOP1 confers resistance to BRAF kinase inhibitors in melanoma by activating MAP kinase pathway

Gupta, R., Bugide, S., Wang, B., Green, M. R., Johnson, D. B., & Wajapeyee, N. (2019) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1821889116 · Cited by 42

Impressive response to dabrafenib, trametinib, and osimertinib in a metastatic EGFR-mutant/BRAF V600E lung adenocarcinoma patient

Ribeiro, M. F. S. A., Knebel, F. H., Bettoni, F., Saddi, R., Sacardo, K. P., Canedo, F. S. N. A., Alessi, J. V. M., Shimada, A. K., Marin, J. F. G., Camargo, A. A., et al. (2021) · npj Precision Oncology · doi:10.1038/s41698-021-00149-4 · Cited by 42

BRAFV600E inhibition stimulates AMP-activated protein kinase-mediated autophagy in colorectal cancer cells

Sueda, T., Sakai, D., Kawamoto, K., Konno, M., Nishida, N., Koseki, J., Colvin, H. S., Takahashi, H., Haraguchi, N., Nishimura, J., et al. (2016) · Scientific Reports · doi:10.1038/srep18949 · Cited by 41

Structural snapshots of RAF kinase interactions

Adariani, S. R., Buchholzer, M., Akbarzadeh, M., Nakhaei‐Rad, S., Dvorský, R., & Ahmadian, M. R. (2018) · Biochemical Society Transactions · doi:10.1042/bst20170528 · Cited by 41

Survival advantage combining a BRAF inhibitor and radiation in BRAF V600E-mutant glioma

Dasgupta, T., Olow, A., Yang, X., Hashizume, R., Nicolaides, T. P., Tom, M. W., Aoki, Y., Berger, M. S., Weiss, W. A., Stalpers, L. J. A., et al. (2015) · Journal of Neuro-Oncology · doi:10.1007/s11060-015-1939-2 · Cited by 41

Advances in the systemic treatment of melanoma brain metastases

Oliva, I. C. G., Schvartsman, G., & Tawbi, H. A. (2018) · Annals of Oncology · doi:10.1093/annonc/mdy185 · Cited by 40

Concurrent HER or PI3K Inhibition Potentiates the Antitumor Effect of the ERK Inhibitor Ulixertinib in Preclinical Pancreatic Cancer Models

Jiang, H., Xu, M., Li, L., Grierson, P. M., Dodhiawala, P. B., Highkin, M. K., Zhang, D., Li, Q., Wang‐Gillam, A., & Lim, K. (2018) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-17-1142 · Cited by 40

Extracellular Signal-Regulated Kinase (ERK) Inhibitors in Oncology Clinical Trials

Chin, H. M., Lai, D. K., & Falchook, G. S. (2019) · Journal of Immunotherapy and Precision Oncology · doi:10.4103/jipo.jipo_17_18 · Cited by 40

Clinical outcome of concomitant vs interrupted BRAF inhibitor therapy during radiotherapy in melanoma patients

Hecht, M., Meier, F. E., Zimmer, L., Polat, B., Loquai, C., Weishaupt, C., Forschner, A., Gutzmer, R., Utikal, J. S., Goldinger, S. M., et al. (2018) · British Journal of Cancer · doi:10.1038/bjc.2017.489 · Cited by 39

LY3214996 relieves acquired resistance to sorafenib in hepatocellular carcinoma cells

Ma, Y., Xu, R., Liu, X., Zhang, Y., Li, S., Qiu, X., Cai, S., Zhou, S., Xie, Y., Li, A., et al. (2021) · International Journal of Medical Sciences · doi:10.7150/ijms.51256 · Cited by 39

Novel induction of CD40 expression by tumor cells with RAS/RAF/PI3K pathway inhibition augments response to checkpoint blockade

Yan, C. W., Saleh, N., Yang, J., Nebhan, C. A., Vilgelm, A. E., Reddy, E. P., Roland, J. T., Johnson, D. B., Chen, S., Shattuck-Brandt, R. L., et al. (2021) · Molecular Cancer · doi:10.1186/s12943-021-01366-y · Cited by 39

ERK Inhibitor LY3214996-Based Treatment Strategies forRAS-Driven Lung Cancer

Köhler, J., Zhao, Y., Li, J., Gokhale, P. C., Tiv, H. L., Knott, A., Wilkens, M. K., Soroko, K. M., Lin, M., Ambrogio, C., et al. (2021) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-20-0531 · Cited by 36

The adjuvant treatment revolution for high-risk melanoma patients

Spagnolo, F., Boutros, A., Tanda, E. T., & Queirolo, P. (2019) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2019.08.024 · Cited by 35

Combination of BRAF Inhibitors and Brain Radiotherapy in Patients With Metastatic Melanoma Shows Minimal Acute Toxicity

Rompoti, N., Schilling, B., Livingstone, E., Griewank, K., Hillen, U., Sauerwein, W. A. G., Pöttgen, C., Stuschke, M., Schadendorf, D., & Zimmer, L. (2013) · Journal of Clinical Oncology · doi:10.1200/jco.2013.50.8473 · Cited by 34

Distinct genomic landscapes of gastroesophageal adenocarcinoma depending on PD-L1 expression identify mutations in RAS–MAPK pathway and TP53 as potential predictors of immunotherapy efficacy

Wang, J., Xiu, J., Baca, Y., Arai, H., Battaglin, F., Kawanishi, N. K., Soni, S., Zhang, W., Millstein, J., Shields, A. F., et al. (2021) · Annals of Oncology · doi:10.1016/j.annonc.2021.03.203 · Cited by 27

Current developments in extracellular-regulated protein kinase (ERK1/2) inhibitors

Niu, Y., & Ji, H. (2022) · Drug Discovery Today · doi:10.1016/j.drudis.2022.01.012 · Cited by 27

The Benefit of Reactivating p53 under MAPK Inhibition on the Efficacy of Radiotherapy in Melanoma

Krayem, M., Sabbah, M., Najem, A., Wouters, A., Lardon, F., Simon, S., Salès, F., Journe, F., Awada, A. H., Ghanem, G., et al. (2019) · Cancers · doi:10.3390/cancers11081093 · Cited by 26

Phase I dose-finding study of oral ERK1/2 inhibitor LTT462 in patients (pts) with advanced solid tumors harboring MAPK pathway alterations.

Jankú, F., Élez, E., Iyer, G., Yamamoto, N., Tan, D. S.-W., Stathis, A., Stammberger, U. M., Evans, H., Seroutou, A., Mais, A., et al. (2020) · Journal of Clinical Oncology · doi:10.1200/jco.2020.38.15_suppl.3640 · Cited by 26

BRAF V600E-dependent role of autophagy in uveal melanoma

Zhao, Y., Wang, W., Min, I., Wyrwas, B., Moore, M., Zarnegar, R., & Fahey, T. J. (2017) · Journal of Cancer Research and Clinical Oncology · doi:10.1007/s00432-016-2317-y · Cited by 26

Transcriptional Activation of Gstp1 by MEK/ERK Signaling Confers Chemo-Resistance to Cisplatin in Lung Cancer Stem Cells

Li, J., Ye, T., Liu, Y., Kong, L., Sun, Z., Liu, D., Wang, J., & Xing, H. (2019) · Frontiers in Oncology · doi:10.3389/fonc.2019.00476 · Cited by 24

Autophagy-Dependent Survival of Mutant B-Raf Melanoma Cells Selected for Resistance to Apoptosis Induced by Inhibitors against Oncogenic B-Raf

Ahn, J.-H., & Lee, M. (2013) · Biomolecules & Therapeutics · doi:10.4062/biomolther.2013.012 · Cited by 23

Regulation of ERK Kinase by MEK1 Kinase Inhibition in the Brain

Tassin, T. C., Benavides, D. R., Plattner, F., Nishi, A., & Bibb, J. A. (2015) · Journal of Biological Chemistry · doi:10.1074/jbc.m115.654897 · Cited by 22

Activated ERK Signaling Is One of the Major Hub Signals Related to the Acquisition of Radiotherapy-Resistant MDA-MB-231 Breast Cancer Cells

Paramanantham, A., Jung, E. J., Go, S., Jeong, B. K., Jung, J., Hong, S., Kim, G. S., & Lee, W. S. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22094940 · Cited by 22

A matching-adjusted indirect comparison of combination nivolumab plus ipilimumab with BRAF plus MEK inhibitors for the treatment of BRAF-mutant advanced melanoma☆

Tarhini, A. A., Toor, K. K., Chan, K., McDermott, D. F., Mohr, P., Larkin, J., Hodi, F. S., Lee, C.-H., Rizzo, J. I., Johnson, H., et al. (2021) · ESMO Open · doi:10.1016/j.esmoop.2021.100050 · Cited by 22

Inhibition of BRAF and ERK1/2 has synergistic effects on thyroid cancer growth in vitro and in vivo

Hicks, H. M., McKenna, L. R., Espinoza, V. L., Pozdeyev, N. V., Pike, L. A., Sams, S. B., LaBarbera, D. V., Reigan, P., Raeburn, C. D., & Schweppe, R. E. (2021) · Molecular Carcinogenesis · doi:10.1002/mc.23284 · Cited by 21

Sorafénib et radiothérapie dans le carcinome hépatocellulaire

Girard, N., & Mornex, F. (2011) · Cancer/Radiothérapie · doi:10.1016/j.canrad.2010.11.012 · Cited by 19

A Phase 2 Clinical Trial of Trametinib and Low-Dose Dabrafenib in Patients with Advanced Pretreated NRASQ61R/K/L Mutant Melanoma (TraMel-WT)

Awada, G., Schwarze, J. K., Tijtgat, J., Fasolino, G., Everaert, H., & Neyns, B. (2021) · Cancers · doi:10.3390/cancers13092010 · Cited by 19

Oncogenic BRAF inhibitor UAI-201 induces cell cycle arrest and autophagy in BRAF mutant glioma cells

Ahn, J., Lee, Y. W., Ahn, S. K., & Lee, M. (2014) · Life Sciences · doi:10.1016/j.lfs.2014.03.026 · Cited by 18

Rational design, synthesis, and biological evaluation of Pan-Raf inhibitors to overcome resistance

Wang, L., Zhu, G., Zhang, Q., Duan, C., Zhang, Y., Zhang, Z., Zhou, Y., Lu, T., & Tang, W. (2017) · Organic & Biomolecular Chemistry · doi:10.1039/c7ob00518k · Cited by 18

TIC10/ONC201: a bend in the road to clinical development

Greer, Y. E., & Lipkowitz, S. (2015) · Oncoscience · doi:10.18632/oncoscience.133 · Cited by 18

Phase I/II Trial of Immunotherapy With Durvalumab and Tremelimumab With Continuous or Intermittent MEK Inhibitor Selumetinib in NSCLC: Early Trial Report

Gaudreau, P.-O., Lee, J. J., Heymach, J. V., & Gibbons, D. L. (2020) · Clinical Lung Cancer · doi:10.1016/j.cllc.2020.02.019 · Cited by 17

Cobimetinib (GDC-0973, XL518)

Andrlová, H., Zeiser, R., & Meiß, F. (2018) · Recent results in cancer research/Recent Results in Cancer Research · doi:10.1007/978-3-319-91442-8_12 · Cited by 16

Vemurafenib Plus Cobimetinib in the Treatment of Mutated Metastatic Melanoma: The CoBRIM Trial

Grimaldi, A. M., Simeone, E., & Ascierto, P. A. (2015) · Melanoma Management · doi:10.2217/mmt.15.22 · Cited by 15

Combination of paclitaxel, bevacizumab and MEK162 in second line treatment in platinum-relapsing patient derived ovarian cancer xenografts

Ricci, F., Guffanti, F., Damia, G. L. M., & Broggini, M. (2017) · Molecular Cancer · doi:10.1186/s12943-017-0662-3 · Cited by 15

A comparative study of the cutaneous side effects between BRAF monotherapy and BRAF/MEK inhibitor combination therapy in patients with advanced melanoma: a single-centre experience

Russo, I., Zorzetto, L., Frigo, A. C., Chiarion‐Sileni, V., & Alaibac, M. (2017) · European Journal of Dermatology · doi:10.1684/ejd.2017.3069 · Cited by 15

The safety and efficacy of cobimetinib for the treatment of BRAF V600E or V600K melanoma

Amaral, T. M. S., Nouri, N., & Garbe, C. (2016) · Expert Review of Anticancer Therapy · doi:10.1080/14737140.2016.1192469 · Cited by 13

Canadian Cancer Trials Group (CCTG) IND215: A phase Ib study of Selumetinib in patients with untreated advanced or metastatic NSCLC who are receiving standard chemotherapy regimens

Goffin, J. R., Nicholas, G. A., Mates, M., Tu, D., CHEN, E., Laurie, S. A., Juergens, R. A., Robinson, A. G., Goss, G. D., Reaume, M. N., et al. (2018) · Investigational New Drugs · doi:10.1007/s10637-018-0680-z · Cited by 13

Contemporary Neoadjuvant Therapies for High-Risk Melanoma: A Systematic Review

Boulva, K., Apte, S. S., Yu, A. M., Tran, A., Shorr, R., Song, X., Ong, M., & Nessim, C. (2021) · Cancers · doi:10.3390/cancers13081905 · Cited by 13

Preclinical studies with ONC201/TIC10 and lurbinectedin as a novel combination therapy in small cell lung cancer (SCLC).

Liguori, N. R., Uruchurtu, A. S. S., Zhang, L., Abbas, A. E., Lee, Y. S., Zhou, L., Azzoli, C. G., & El‐Deiry, W. S. (2022) · PubMed Central · Cited by 13

Dabrafenib plus trametinib in patients with BRAFV600E-mutated biliary tract cancer

van Golen, R. F., & Dekker, T. J. A. (2020) · The Lancet Oncology · doi:10.1016/s1470-2045(20)30554-4 · Cited by 13

Targeting the RAS/RAF/MAPK pathway for cancer therapy: from mechanism to clinical studies

Bahar, M. E., Kim, H. J., & Kim, D. R. (2023) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-023-01705-z · Cited by 888

Navigating the ERK1/2 MAPK Cascade

Martín-Vega, A., & Cobb, M. H. (2023) · Biomolecules · doi:10.3390/biom13101555 · Cited by 127

Oxidative Stress and Cancer Therapy: Controlling Cancer Cells Using Reactive Oxygen Species

Ju, S., Singh, M. K., Han, S., Ranbhise, J. S., Ha, J., Choe, W., Yoon, K., Yeo, S. G., Kim, S. S., & Kang, I. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms252212387 · Cited by 133

Roles and inhibitors of FAK in cancer: current advances and future directions

Hu, H.-H., Wang, S., Shang, H.-L., Lv, H., Chen, B., Gao, S., & Chen, X. (2024) · Frontiers in Pharmacology · doi:10.3389/fphar.2024.1274209 · Cited by 100

Heat shock proteins as hallmarks of cancer: insights from molecular mechanisms to therapeutic strategies

Zuo, W., Pang, Q., Zhu, X., Yang, Q., Zhao, Q., He, G., Han, B., & Huang, W. (2024) · Journal of Hematology & Oncology · doi:10.1186/s13045-024-01601-1 · Cited by 108

Targeting the MAPK–RAS–RAF signaling pathway in cancer therapy

Santarpia, L., Lippman, S. M., & El‐Naggar, A. K. (2012) · Expert Opinion on Therapeutic Targets · doi:10.1517/14728222.2011.645805 · Cited by 1,082

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

Targeting the Raf-MEK-ERK Mitogen-Activated Protein Kinase Cascade for the Treatment of RAS Mutant Cancers

Hayes, T. K., & Der, C. J. (2014) · Springer eBooks · doi:10.1007/978-3-7091-1806-1_6 · Cited by 6

Targeting the RAF–MEK–ERK pathway in cancer therapy

Montagut, C. O., & Settleman, J. (2009) · Cancer Letters · doi:10.1016/j.canlet.2009.01.022 · Cited by 466

Stamping out RAF and MEK1/2 to inhibit the ERK1/2 pathway: an emerging threat to anticancer therapy

Mandal, R., Becker, S., & Strebhardt, K. (2015) · Oncogene · doi:10.1038/onc.2015.329 · Cited by 93