Cited by 557Melanoma and MAPK PathwaysProtein Kinase Regulation and GTPase SignalingProtein Tyrosine Phosphatases

The DOI matches its Crossref record; 489 of the 506 references it cites were found in a registry or an index.

RAF-MEK-ERK pathway in cancer evolution and treatment

Ullah, Rahim, Yin, Qing, Snell, Aidan H., Wan, Lixin·2022·Seminars in Cancer Biology

DOI 10.1016/j.semcancer.2021.05.010

Open this paper in CoChat — free account

Abstract

The RAF-MEK-ERK signaling cascade is a well-characterized MAPK pathway involved in cell proliferation and survival. The three-layered MAPK signaling cascade is initiated upon RTK and RAS activation. Three RAF isoforms ARAF, BRAF and CRAF, and their downstream MEK1/2 and ERK1/2 kinases constitute a coherently orchestrated signaling module that directs a range of physiological functions. Genetic alterations in this pathway are among the most prevalent in human cancers, which consist of numerous hot-spot mutations such as BRAF V600E. Oncogenic mutations in this pathway often override otherwise tightly regulated checkpoints to open the door for uncontrolled cell growth and neoplasia. The crosstalk between the RAF-MEK-ERK axis and other signaling pathways further extends the proliferative potential of this pathway in human cancers. In this review, we summarize the molecular architecture and physiological functions of the RAF-MEK-ERK pathway with emphasis on its dysregulations in human cancers, as well as the efforts made to target the RAF-MEK-ERK module using small molecule inhibitors.

Integrity signals

Registry

Crossref · 10.1016/j.semcancer.2021.05.010

Cites

489 of 489 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Claims the paper makes

This paper’s full text isn’t openly available, so its claims and self-check weren’t run. The registry and citation checks still apply.

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?

Hallmarks of Cancer: The Next Generation
Hanahan, D., & Weinberg, R. A. (2011) · Cell · doi:10.1016/j.cell.2011.02.013 · Cited by 66,590
The cBio Cancer Genomics Portal: An Open Platform for Exploring Multidimensional Cancer Genomics Data
Cerami, E., Gao, J., Dogrusoz, U., Gross, B. E., Sumer, S. O., Aksoy, B. A., Jacobsen, A., Byrne, C. J., Heuer, M. L., Larsson, E., et al. (2012) · Cancer Discovery · doi:10.1158/2159-8290.cd-12-0095 · Cited by 17,455
On the origin of cancer cells
Warburg, O. (1956) · Science · doi:10.1126/science.123.3191.309 · Cited by 13,425
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
Cell Signaling by Receptor Tyrosine Kinases
Lemmon, M. A., & Schlessinger, J. (2010) · Cell · doi:10.1016/j.cell.2010.06.011 · Cited by 7,929
mTOR Signaling in Growth, Metabolism, and Disease
Saxton, R. A., & Sabatini, D. M. (2017) · Cell · doi:10.1016/j.cell.2017.02.004 · Cited by 7,555
ras oncogenes in human cancer: a review.
Bos, J. L. (1989) · PubMed · Cited by 5,061
AMPK: guardian of metabolism and mitochondrial homeostasis
Herzig, S., & Shaw, R. J. (2017) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm.2017.95 · Cited by 4,192
Mitogen-Activated Protein (MAP) Kinase Pathways: Regulation and Physiological Functions*
Pearson, G. W., Robinson, F. L., Gibson, T. B., Xu, B.-E., Karandikar, M. S., Berman, K. S., & Cobb, M. H. (2001) · Endocrine Reviews · doi:10.1210/edrv.22.2.0428 · Cited by 4,111
BAY 43-9006 Exhibits Broad Spectrum Oral Antitumor Activity and Targets the RAF/MEK/ERK Pathway and Receptor Tyrosine Kinases Involved in Tumor Progression and Angiogenesis
Wilhelm, S. M., Carter, C., Tang, L., Wilkie, D. P., McNabola, A., Rong, H., Chen, C., Zhang, X., Vincent, P. W., McHugh, M., et al. (2004) · Cancer Research · doi:10.1158/0008-5472.can-04-1443 · Cited by 4,060

Flagged first, then by citations

Show all 506 references

17 of the 506 references couldn’t be matched to a known paper.

Research works printed but not linked: 1

Pagès, 1999, Defective thymocyte maturation in p44 MAP kinase (Erk 1) knockout mice, Science, 286, 1374, 10.1126/science.286.5443.1374 · DOI · Paper page

Sorted by citations

Items 401–500 of 557

Identification of a novel molecular classification for hepatocellular carcinoma based on disulfideptosis-related genes and its potential prognostic significance
Wang, T., Liu, Y., Kong, J., & Liu, J. (2024) · Journal of Cancer Research and Clinical Oncology · doi:10.1007/s00432-024-06031-7
Integrating multi-omics methods for personalized treatment of refractory chronic myelomonocytic leukemia with NRAS and TET2 mutations
Hou, C., Yang, B., Wang, Y., Cai, L., Qin, R., Guo, B., Geng, J., & Lu, X. (2024) · Cancer Pathogenesis and Therapy · doi:10.1016/j.cpt.2024.12.001
“7,8 Trametinib, a speci ﬁ c MEK inhibitor, is commonly used to treat unresectable or metastatic melanomas harboring BRAFV600E and V600K mutations.”
Lupeol: Bioactivity-guided cytotoxic principle from Hymenocardia acida Tul. (Phyllantaceae) suppresses signaling pathways via polypharmacology antagonism
Adedokun, O. A., Ayinde, B. A., Maggi, F., & Barboni, L. (2024) · South African Journal of Botany · doi:10.1016/j.sajb.2024.12.007
Positive feedback loop between NRASQ61R mutation and RAB27B expression in endothelial cells
Li, Z., Cai, Y., Wang, T., Peng, S., Zhao, J., Tong, W., & Ren, J. (2025) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2025.151422
The mechanism of E3 ubiquitin ligase HERC1 regulating ferroptosis in lung adenocarcinoma cells
Ye, F., Xu, Y., Zhu, X., Ding, Q., Wang, Y., Lu, S., & Chen, Y. (2025) · Cancer Genetics · doi:10.1016/j.cancergen.2025.02.001
Lactobacillus brevis YNH inhibits proliferation of HeLa cells and promotes their apoptosis by modulating the PI3K/AKT pathway
He, L., Tan, D., Zhu, R., Zhao, J., Yin, H., Duan, M., Li, X., Fan, W., Yang, Z., Wang, X., et al. (2025) · Współczesna Onkologia · doi:10.5114/wo.2025.148642
“Ras/Raf/ERK, JNK, p38/MAPK, and ERK are four subpathways within the MAPK pathway that play roles in tumour development [57, 58].”
Construction of Lung Adenocarcinoma Xenograft Model in Mice and Evaluation of the Efficiency of XY Decoction through MAPK Pathway
Wang, Y., Wang, T., Wang, Z., Wang, K., Wu, D., Song, S., & Chen, M. (2025) · Journal of Visualized Experiments · doi:10.3791/68023
In situ multifunctional gel for hormone-immune therapy of ovarian cancer and prevention of postoperative adhesion
Zhang, Y., Shi, Y., Zang, H., Zhao, X., Fu, X., Qiu, S., Zhang, Y., Liu, Y., Wan, X., Li, Z., et al. (2025) · Chemical Engineering Journal · doi:10.1016/j.cej.2025.163135
Blood metabolites, protein regulatory networks and their roles in pan-cancer: a mendelian randomisation study
Xia, S., Xu, Z., Cheng, C., An, R., Chen, W., Lin, D., Gao, Y., Wang, L., Xie, X., & Zhang, J. (2025) · Discover Oncology · doi:10.1007/s12672-025-02522-2
“Cancer is characterized by dysregulation of key cellular processes, including kinase-mediated apoptotic pathways such as MAPKs (p38, JNK), PI3K, and AKT, which are critical for regulating cell death and metabolic activities [27, 28].”
Pharmacodynamics of huaier aqueous extract against papillary thyroid carcinoma in vivo and in vitro
Xu, F., Zheng, L.-L., Qin, J., Li, Y.-X., Chen, K.-H., Dai, L.-H., Zhu, Q., & Sang, J. (2025) · Integrative Cancer Therapies · doi:10.1177/15347354251339073
PLAC8 as a potential therapeutic target for myocardial infarction: unraveling the molecular mechanisms
Tong, Y., Huang, X., Qian, W., & Liu, L. (2025) · Journal of Physiology and Biochemistry · doi:10.1007/s13105-025-01098-3
Immunosuppressive MAP3K11 as an independent risk factor for progression-free survival promotes prostate cancer metastasis by regulating epithelial-mesenchymal transition
Zhang, Z., Zeng, G., Wu, H., Dong, W., Huang, Y., Feng, X., Li, X., Tang, K., Xiao, M., & SU, Z. (2025) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2025.152172
A computational framework for the design and development of ERK2 and multi-target ERK2/HDAC inhibitors
Čebzan, A., Ružić, D., Djoković, N., Stanković, B., & Nikolic, K. M. (2025) · Computational Biology and Chemistry · doi:10.1016/j.compbiolchem.2025.108543
A novel synergistic drug combination of a mitogen-activated extracellular signal-regulated kinase inhibitor with [177Lu]Lu-rhPSMA-10.1 for prostate cancer treatment: Results of a preclinical evaluation
Foxton, C., Cornelissen, B. T., O’Neill, E. S., Waldron, B. P., Pretzmann, F., Grønlund, R. V., Hallund, M. W., & Stevens, D. J. (2025) · Nuclear Medicine and Biology · doi:10.1016/j.nucmedbio.2025.109042
Oncogenic Activity and Sorafenib Sensitivity of ARAF p.S214C Mutation in Lung Cancer
Lee, C., Mu, W., Chen, X., Chan, M. S. M., Chen, Z., Yeung, S. F., Chan, H. H. Y., Chow, S. T., Ko, B. C. B., Chan, D. W., et al. (2025) · Cancers · doi:10.3390/cancers17132246
“…Raf-MEK-ERK signaling pathway and demonstrated enhanced oncogenic potential in terms of cell proliferation, colony and spheroid formation efficiency, and migration and invasion capabilities, which aligns with previous findings that underscore the critical role of this pathway in tumorigenesis [5].”
SPTLC2 Negatively Regulates Neural Stem Cell Activity and Proliferation via Inhibition of the MEK/ERK Signaling: Insights into the Molecular Mechanisms Underlying Neural Stem Cell BehaviorPreprint
Liu, T., Lan, F., Huang, J., Ye, Y., & Su, X. (2025) · Research Square · doi:10.21203/rs.3.rs-7137060/v1
RETRACTED ARTICLE: PGRP-S promotes hepatocellular carcinoma progression via MAPK/ERK pathway by interaction with TTC1
Zhu, H., Feng, S., Lv, S., Zhao, D., Chang, X., Fan, S., Wang, X., & Qian, X. (2025) · Scientific Reports · doi:10.1038/s41598-025-12160-x
“In many mammalian cell types, Mitogen-activated protein kinase (MAPK) plays a key role in integrating external signals bound by signaling molecules and cell surface receptors into signaling events that promote cell growth and proliferation through the MAPK/ERK pathway 34 .”
Retracted
Centrosome‐Signaling Pathway Crosstalk: A Core Hub From Cellular Homeostasis to Disease
Pan, M., Li, J., & Fu, J. (2025) · Cytoskeleton · doi:10.1002/cm.70027
WITHDRAWN: Oncolytic HSV-CD44 Reprograms One-Carbon Metabolism to Modulate AKT and MAPK Signaling in Glioblastoma Stem CellsPreprint
Luo, Y., Feng, F., Bu, T., Cai, X., Chen, H., Yang, Z., Wu, K., & Li, Y. (2025) · Research Square · doi:10.21203/rs.3.rs-7111399/v1
Molecular crossroads: identifying MAPK proteins bridging SMAD and dopamine pathways in breast cancer
Borawski, P., Sirek, T., Sirek, A., Zmarzły, N., Nowakowski, R., Ossowski, P., Chalcarz, M., Boroń, K., Boroń, D., Bereza, K., et al. (2025) · Cell Cycle · doi:10.1080/15384101.2025.2549097
“Our findings underscore the central role of the MAPK pathway as a molecular hub integrating signals from multiple oncogenic pathways [56].”
Comprehensive pan-cancer analysis and experimental validation of TRAP1 as a possible medicinal targetPreprint
Shan, S., Wang, T., Sun, F., Liang, S., Zhao, L., & Wang, Z. (2025) · Research Square · doi:10.21203/rs.3.rs-7381783/v1
Identification and validation of cell senescence genes in recurrent spontaneous abortion via multiple bioinformatics algorithms
Wei, Y., Zhou, Z., Wei, C., Cheng, J., Lin, S., Zhu, Z., & Pang, L. (2025) · Scientific Reports · doi:10.1038/s41598-025-19251-9
“This pathway is associated with various diseases, including cancer, inflammatory diseases, and neurodegenerative diseases 49–51 .”
Medicinal chemistry perspective of ERK1/2 inhibitors in cancer treatment: an updated patent review (2019–present)
Singh, A. K., Chauhan, A., Prajapati, V., Kumar, A., Singh, H., Verma, A., & Kumar, P. (2025) · Expert Opinion on Therapeutic Patents · doi:10.1080/13543776.2025.2575028
“As critical components of the MAPK signaling cascade, ERK1/2 plays a pivotal role in numerous cellular processes and disease mechanisms, making it an attractive target in therapeutic development [84].”
Genetic variation in targets of granulocyte colony-stimulating factor drugs and 14 cancers risk: A Mendelian randomization study
Zhou, H., Yan, S., Guo, J., Yang, X., & Huang, T. C. (2025) · Medicine · doi:10.1097/md.0000000000045485
“[6–9] Due to potential confounding and reverse causality, observational studies can only establish associations, not causal relationships.”
Multidimensional analysis of hsa-miR-140-3p and CKS1B correlation via the MAPK/ERK pathway in lung adenocarcinoma progression
Luo, K., Liu, M., Song, Y., Zhao, H., Cai, Y., Chen, S., Lei, Y., Ma, D., Zhang, H., & Zhao, Y. (2025) · Discover Oncology · doi:10.1007/s12672-025-03768-6
“Notably, the mitogen-activated protein MAPK/ERK pathway—a central regulator of cell proliferation, differentiation, and survival—has been implicated in LUAD progression, but its relationship with CKS1B expression has not been fully characterized [13].”
Dihydroartemisinin downregulates the expression of COX-2 in esophageal squamous cell carcinoma through ROS/MAPK/Sp1 axisPreprint
Liao, C., Ma, Q., Yang, Y., Zhu, J., Liu, X., Tang, M., Luo, M., Zhong, X., Xu, L., Liao, H., et al. (2025) · Research Square · doi:10.21203/rs.3.rs-7882728/v1
Mechanisms of lncRNA in Diabetic Foot Ulcer Wound Healing
Chen, Y., Wang, M., Cao, X., Gao, S., Jiang, Y., & Gong, Z. (2025) · The Journal of Gene Medicine · doi:10.1002/jgm.70050 · Cited by 2
RPL17 regulates the progression of breast cancer accompanied by MAPK signaling activation
Cai, Y., Liu, H., & Yin, G. (2025) · Medical Oncology · doi:10.1007/s12032-025-03117-1
Nanotechnology in gynaecological cancers: Biomedical perspectives on lipid-based drug delivery systems for targeted therapy
Suthar, R., Yadav, R., Kumari, P., & Mehra, N. K. (2025) · International Journal of Pharmaceutics · doi:10.1016/j.ijpharm.2025.126402
Characterizing drug activity with sensitive interactomes in human living cellsPreprint
Kundlacz, C., Sleiman, N. H., Marmigère, F., Gillet, B., Hughes, S., Gilquin, L., Duplus‐Bottin, H., Dumont, A., Yvert, G., Bleicher, F., et al. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.11.20.689448
Turning the Tables: How Encorafenib and Binimetinib are Reshaping NSCLC Treatment
Khoury, J., Boutros, M., Attieh, F., & Kourié, H. R. (2025) · Cancer Investigation · doi:10.1080/07357907.2025.2595301
BRAP Promotes the Tumorigenesis of Hepatocellular Carcinoma by Corrupting Cancer Cell Cycle Regulation and Enhancing Immune Evasion
Guo, Y., Gu, R., Gao, F., Liu, L., Deng, D., Zhang, Q., Wang, L., Liu, Q., Lan, L., & Cang, S. (2025) · Journal of Hepatocellular Carcinoma · doi:10.2147/jhc.s547105
“19 An in-depth analysis of our RNA-Seq data through GSEA revealed a significantly enrichment of BRAP-associated genes within the MAPK/ERK signaling pathway (Figure 7A and B).”
Endoplasmic reticulum stress upregulate HYOU1 and mediates lenvatinib resistance in liver cancer through ERK/MAPK pathway
Du, X., Jiang, W., Yan, S., Chen, X., Wang, A., Liu, J., Fan, L., Huang, Y.-H., Zu, X., & Sun, G. (2025) · MedScience · doi:10.1007/s11684-025-1173-z
Additional file 1 of A positive feedback loop between PFKP and c-Myc drives head and neck squamous cell carcinoma progression
Liu, W., Ding, Z., Tao, Y., Liu, S., Jiang, M., Yi, F., Wang, Z., Han, Y., Zong, H., Li, D., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26231148
Additional file 11 of A positive feedback loop between PFKP and c-Myc drives head and neck squamous cell carcinoma progression
Liu, W., Ding, Z., Tao, Y., Liu, S., Jiang, M., Yi, F., Wang, Z., Han, Y., Zong, H., Li, D., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26747141
Additional file 3 of Domperidone inhibits cell proliferation via targeting MEK and CDK4 in esophageal squamous cell carcinoma
Yuan, Q., Shi, Y., Zhang, Y., Shi, Y., Hussain, Z., Zhao, J., jiang, Y., Qiao, Y., Guo, Y., Lu, J., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26697581
Additional file 10 of A positive feedback loop between PFKP and c-Myc drives head and neck squamous cell carcinoma progression
Liu, W., Ding, Z., Tao, Y., Liu, S., Jiang, M., Yi, F., Wang, Z., Han, Y., Zong, H., Li, D., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26747138
Additional file 12 of A positive feedback loop between PFKP and c-Myc drives head and neck squamous cell carcinoma progression
Liu, W., Ding, Z., Tao, Y., Liu, S., Jiang, M., Yi, F., Wang, Z., Han, Y., Zong, H., Li, D., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26747144
Additional file 7 of A positive feedback loop between PFKP and c-Myc drives head and neck squamous cell carcinoma progression
Liu, W., Ding, Z., Tao, Y., Liu, S., Jiang, M., Yi, F., Wang, Z., Han, Y., Zong, H., Li, D., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26747129
Additional file 2 of Domperidone inhibits cell proliferation via targeting MEK and CDK4 in esophageal squamous cell carcinoma
Yuan, Q., Shi, Y., Zhang, Y., Shi, Y., Hussain, Z., Zhao, J., jiang, Y., Qiao, Y., Guo, Y., Lu, J., et al. (2024) · Figshare · doi:10.6084/m9.figshare.25479109
Additional file 16 of A positive feedback loop between PFKP and c-Myc drives head and neck squamous cell carcinoma progression
Liu, W., Ding, Z., Tao, Y., Liu, S., Jiang, M., Yi, F., Wang, Z., Han, Y., Zong, H., Li, D., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26747156
Additional file 14 of A positive feedback loop between PFKP and c-Myc drives head and neck squamous cell carcinoma progression
Liu, W., Ding, Z., Tao, Y., Liu, S., Jiang, M., Yi, F., Wang, Z., Han, Y., Zong, H., Li, D., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26747150
Additional file 15 of A positive feedback loop between PFKP and c-Myc drives head and neck squamous cell carcinoma progression
Liu, W., Ding, Z., Tao, Y., Liu, S., Jiang, M., Yi, F., Wang, Z., Han, Y., Zong, H., Li, D., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26747153
Additional file 17 of A positive feedback loop between PFKP and c-Myc drives head and neck squamous cell carcinoma progression
Liu, W., Ding, Z., Tao, Y., Liu, S., Jiang, M., Yi, F., Wang, Z., Han, Y., Zong, H., Li, D., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26747159
Additional file 2 of A positive feedback loop between PFKP and c-Myc drives head and neck squamous cell carcinoma progression
Liu, W., Ding, Z., Tao, Y., Liu, S., Jiang, M., Yi, F., Wang, Z., Han, Y., Zong, H., Li, D., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26231298
Additional file 9 of A positive feedback loop between PFKP and c-Myc drives head and neck squamous cell carcinoma progression
Liu, W., Ding, Z., Tao, Y., Liu, S., Jiang, M., Yi, F., Wang, Z., Han, Y., Zong, H., Li, D., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26747135
Additional file 3 of A positive feedback loop between PFKP and c-Myc drives head and neck squamous cell carcinoma progression
Liu, W., Ding, Z., Tao, Y., Liu, S., Jiang, M., Yi, F., Wang, Z., Han, Y., Zong, H., Li, D., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26747117
Additional file 5 of Domperidone inhibits cell proliferation via targeting MEK and CDK4 in esophageal squamous cell carcinoma
Yuan, Q., Shi, Y., Zhang, Y., Shi, Y., Hussain, Z., Zhao, J., jiang, Y., Qiao, Y., Guo, Y., Lu, J., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26697587
Additional file 1 of Domperidone inhibits cell proliferation via targeting MEK and CDK4 in esophageal squamous cell carcinoma
Yuan, Q., Shi, Y., Zhang, Y., Shi, Y., Hussain, Z., Zhao, J., jiang, Y., Qiao, Y., Guo, Y., Lu, J., et al. (2024) · Figshare · doi:10.6084/m9.figshare.25478754
Additional file 5 of A positive feedback loop between PFKP and c-Myc drives head and neck squamous cell carcinoma progression
Liu, W., Ding, Z., Tao, Y., Liu, S., Jiang, M., Yi, F., Wang, Z., Han, Y., Zong, H., Li, D., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26747123
Additional file 13 of A positive feedback loop between PFKP and c-Myc drives head and neck squamous cell carcinoma progression
Liu, W., Ding, Z., Tao, Y., Liu, S., Jiang, M., Yi, F., Wang, Z., Han, Y., Zong, H., Li, D., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26747147
Additional file 4 of Domperidone inhibits cell proliferation via targeting MEK and CDK4 in esophageal squamous cell carcinoma
Yuan, Q., Shi, Y., Zhang, Y., Shi, Y., Hussain, Z., Zhao, J., jiang, Y., Qiao, Y., Guo, Y., Lu, J., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26697584
Additional file 6 of Domperidone inhibits cell proliferation via targeting MEK and CDK4 in esophageal squamous cell carcinoma
Yuan, Q., Shi, Y., Zhang, Y., Shi, Y., Hussain, Z., Zhao, J., jiang, Y., Qiao, Y., Guo, Y., Lu, J., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26697590
Additional file 4 of A positive feedback loop between PFKP and c-Myc drives head and neck squamous cell carcinoma progression
Liu, W., Ding, Z., Tao, Y., Liu, S., Jiang, M., Yi, F., Wang, Z., Han, Y., Zong, H., Li, D., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26747120
Additional file 1 of Valtrate, an iridoid compound in Valeriana, elicits anti-glioblastoma activity through inhibition of the PDGFRA/MEK/ERK signaling pathway
Liu, X., Hu, Y., Xue, Z., Zhang, X., Liu, X., Liu, G., Wen, M., Chen, A., Huang, B., Li, X., et al. (2023) · Figshare · doi:10.6084/m9.figshare.22612796
Additional file 8 of A positive feedback loop between PFKP and c-Myc drives head and neck squamous cell carcinoma progression
Liu, W., Ding, Z., Tao, Y., Liu, S., Jiang, M., Yi, F., Wang, Z., Han, Y., Zong, H., Li, D., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26747132
Additional file 6 of A positive feedback loop between PFKP and c-Myc drives head and neck squamous cell carcinoma progression
Liu, W., Ding, Z., Tao, Y., Liu, S., Jiang, M., Yi, F., Wang, Z., Han, Y., Zong, H., Li, D., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26747126
Additional file 1 of Low TYROBP expression predicts poor prognosis in multiple myeloma
Luo, H., Pan, C., Wang, L., Zheng, L., Cao, S., Hu, X., Hu, T., Zhao, N., Shang, Q., & Wang, J. (2024) · Figshare · doi:10.6084/m9.figshare.26699327
NPSR1-AS1 Promotes Colorectal Cancer Cell Proliferation by Upregulating YRDC Expression via Interaction with miR-365b-3p
Li, G., Wang, Y., Lu, Y., Chen, W. X., Kang, X., Han, Z., & Liu, M. (2025) · The Tohoku Journal of Experimental Medicine · doi:10.1620/tjem.2025.j139
ECSCR functions as a potential tumor suppressor in breast cancer cells
Lian, S., Huang, Y., Liang, L., Yang, Y., Mo, Y., Wang, S., & Wei, C. (2025) · Medical Oncology · doi:10.1007/s12032-025-03228-9
“Given that the RAF-MEK-ERK pathway regulates critical cellular processes including proliferation, differentiation, and apop - tosis [24], these results suggest that ECSCR overexpression inhibits breast cancer cell proliferation, potentially via suppression of the RAF-MEK-ERK pathway in TNBC.”
Клинические исходы и молекулярные детерминанты серозного рака яичников низкой степени злокачественности: результаты исследования и обзор литературы
Матылевич, О. П., Тарасов, И. А., Мавричев, С. А., Доломанова, Е. В., Ровский, Д. В., Бакиновская, И. Е., & Martsinkevich, A. F. (2025) · Евразийский онкологический журнал · doi:10.34883/pi.2025.13.4.022
Design, synthesis of 2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indole derivatives as potential anticancer agents
Xu, Y. C., Sun, Y., Yu, Z., Zhang, X., Liu, Z., Xin, J., Liu, S., & Zhao, F. (2026) · Bioorganic & Medicinal Chemistry Letters · doi:10.1016/j.bmcl.2026.130535
HAX1 overexpression induces osteogenic differentiation of periodontal ligament stem cells via the MEK/ERK signaling cascade
Hao, P., Zhang, X., Wang, M., Bao, F., & Guo, H. (2026) · Tissue and Cell · doi:10.1016/j.tice.2026.103311
Molecular basis of mitogen-activated protein kinase ERK2 activation by its upstream kinase MEK1Preprint
von Velsen, J., Juyoux, P., Piasentin, N., Fisher, H., Lapouge, K., Vadas, O., Gervasio, F. L., & Bowler, M. W. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.01.19.700303
The P7 peptide antagonizes bFGF-induced malignant behaviors of ovarian cancer by inhibiting MEK/ERK signaling pathway
Yang, Z., Wei, W. J., Nie, D., Zhang, M., & Chen, Q. (2026) · Future Science OA · doi:10.1080/20565623.2026.2615619
“…a central player in Oc development and progression. this pathway regulates a broad range of biological processes, such as cell proliferation, apoptosis, cell cycle progression, metabolic reprogramming, and cell migration and invasion, all of which are closely linked to tumor aggressiveness [9,10].”
Mechanistic insights into dietary CuO nanoparticle (CuO NP)-induced hepatic lipotoxicity: the critical role of the Ccs/Mek1/Erk1/2/Pparα pathway and mitochondrial oxidative stress
Yang, H., Zhao, P., Wei, X., Huang, C., Lv, W.-H., Zhou, Y.-C., & Luo, Z. (2026) · Environmental Science Nano · doi:10.1039/d5en01152c
HER2/neu Expression in Low-Grade Serous Ovarian Carcinoma: A Pilot Two-Center Retrospective Study
Станиславовна, Б. А., Asaturova, A. V., Rogozhina, A., Ezhova, E. L. S., Arzhanukhina, N. A., Tregubova, A., Викторович, Р. Д., & Sukhikh, G. T. (2026) · Journal of Clinical Medicine · doi:10.3390/jcm15031038
“Promising case studies and clinical trials involving medications such as anastrozole, cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors, and EGFR inhibitors have resulted from these discoveries [14–18].”
Unveiling a BRAF Signature Proficient in Accurately Capturing Oncogenic Activity and Guiding Prognostic Prediction Across Multiple Cancers
Yang, K., Fu, S., Liang, J., Ding, L., You, J., Li, F., Yuan, Y., & Bian, X.-W. (2026) · MedComm · doi:10.1002/mco2.70591
The small Rho GTPase Rif promotes cancer progression through ERK2-mediated epithelial-mesenchymal transition
Zhao, H., Wu, M., Bai, X., Wang, J., Morigen, M., & Fan, L. (2026) · Acta Biochimica et Biophysica Sinica · doi:10.3724/abbs.2026019
System-Level Biological Evaluation of Flaxseed Intake on Sleep Regulation
Gonzalez, M., Ruiz, J., Torres, L., & Mendez, C. (2021) · Specialty journal of Pharmacognosy Phytochemistry and Biotechnology · doi:10.51847/9adby2ansl
ASH2L induces tamoxifen resistance via H3K4me3 dependent ITGA6/ERK signaling in ER-positive breast cancer
Kye, Y.-H., Moon, S., Cha, H.-R., Kim, T., Eom, J. Y., Myung, J., & Kong, G. (2026) · British Journal of Cancer · doi:10.1038/s41416-026-03347-8
“ERK signalling is involved in tumorigenesis in human cancers, including ovarian and breast cancer [61 – 63].”
Discovery of Novel and Potent Dual PARP1/ERK Inhibitors as a Promising Strategy for Cancer Therapy
Bai, Y., Wu, S., Zhang, W., Chen, Y., Yan, W., Huang, L., Liu, J., Guan, Z., Su, Y., Guo, D., et al. (2026) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.6c00001
SEC14L4 promotes the development of esophageal squamous cell cancer by inhibiting the ubiquitination and degradation of DDX3X via RNF39
Huang, D., Wang, D., Wang, Y., Wang, X., He, C., Du, Y., Ma, Q., Chen, X., & Wang, A. (2026) · Oncogene · doi:10.1038/s41388-026-03700-4
CSDE1 Drives Glycolysis and the Progression of Prostate Cancer Through RAC1 ‐Dependent RAS / MAPK Activation
Yin, Z., Wang, Z., Gong, W., Wang, Z., Li, Z., Xu, L., Ning, J., Gao, L., Pan, T., Yu, W., et al. (2026) · The FASEB Journal · doi:10.1096/fj.202504006r
ALOX15 exerts tumor-suppressive role in head and neck squamous cell carcinoma via ERK pathway
Liu, A., Zhang, X., Li, R., Zhang, Y., Yang, Z., Zou, D., Ji, X., & Hong, L. (2026) · Functional & Integrative Genomics · doi:10.1007/s10142-026-01838-8
“Meanwhile, the extracellular signal-regulated kinase (ERK) pathway—a central signaling cascade—plays critical roles in regulating cell proliferation, survival, differentiation, and migration (Park 2023; Ullah et al. 2022).”
Data Mining of Key Quality Components from NATCM- Registered BPH Prescriptions, Their Quantification and Activity Optimization
Xu, F., Wu, J., Fang, H., Yang, L., Qu, A., Qin, H., Liu, T., Li, J., Zheng, S., Ruan, X., et al. (2026) · Natural Product Communications · doi:10.1177/1934578x261431537
“24 STAT3 plays a critical role in modulating genes involved in cellular growth and programed cell death.”
The MEK1/2-IRF4 axis fosters T follicular helper cell differentiationand antitumor humoral immune response
Ran, S., Wang, S., Li, R., Lai, L., Yu, J., Zhang, X., Li, Y., Ye, W., Zong, J., Li, X., et al. (2026) · Journal of Translational Medicine · doi:10.1186/s12967-026-08023-2 · Cited by 1
“Given that MEK1/2 inhibitors are widely used in clinical treatment [73], we next assessed the correlation between the main cellular subpopulations involved in the humoral immune response and the clinical features of melanoma patients (Fig.”
A computational rule-based model of MAPK/ERK system regulation
Kocieniewski, P., & Lipniacki, T. (2026) · Scientific Reports · doi:10.1038/s41598-026-44353-3
X‐Linked Inhibitor of Apoptosis Protein (XIAP) Contributes to ERK1/2‐Mediated Anoikis Resistance in Hepatocellular Carcinoma
Zeng, Q., Mao, Z., Sun, S., Gao, Z., Mu, J., Pan, Z., Li, Q., Mao, X., Xu, J., Bai, D., et al. (2026) · MedComm – Oncology · doi:10.1002/mog2.70059
“MKK1/2 is a dual-specificity kinase known for activating ERK1/2 in cancer [44].”
Abrine targets ERK to suppress EMT and lung metastasis model via MAPKs and Nrf2/Keap-1/HO-1 signaling
Yufang, S. H. E. N., Xiao, L., Liu, L., Lianting, L. I. A. O., Zou, X., Shen, P., Zhao, J., Yuan, R., Gao, H., & Yao, C. (2026) · Frontiers in Immunology · doi:10.3389/fimmu.2026.1789110
“The MAPKs/ERK pathway is a key regulatory factor for EMT (20, 21).”
A novel AGTPBP1-ERK/MYLK network mediates pancreatic cancer progression
Yang, Z.-Y., Zhang, Q., Yang, J., Zhang, X.-D., Liu, C.-L., Huang, J.-Y., Xiao, R., & Ren, J.-J. (2026) · Tissue and Cell · doi:10.1016/j.tice.2026.103512
Dephosphorylation of C20orf112 by PPP3CA/PPIA drives its nuclear translocation to promote colorectal cancer stemness
Wang, X.-X., Pan, E.-G., Zeng, Y.-H., Gao, G., Wang, W.-N., Huang, R., Fan, Z.-H., Zhong, J.-R., Zheng, Y.-S., He, Q., et al. (2026) · International Journal of Biological Macromolecules · doi:10.1016/j.ijbiomac.2026.151735
CAPG serves as a prognostic biomarker and promotes proliferation and migration in pancreatic ductal adenocarcinoma
Qin, Z., Li, K., Li, X., Wang, H., & Zhang, Y. (2026) · PLoS ONE · doi:10.1371/journal.pone.0346011
“Multiple studies have indicated that excessive or inappropriate activation of the ERK pathway is implicated in the initiation and progression of human cancers [27–29].”
A nanobody based approach to capture interactomes of dimeric protein complexes in living cells
Sleiman, N. H. (2024) · theses.fr (ABES) · doi:10.70675/633151e1z9a1cz42b0zbcbaz776177601937
Translational control in ovarian cancer : role of the glutaminyl-tRNA synthetase QARS in DNA damage response
Serafini, M. (2024) · theses.fr (ABES) · doi:10.70675/ab8b1f5az3c15z4b5fzba28z247b40b8c7e0
GMFB promotes lung adenocarcinoma progression by activating the MAPK/ERK signaling pathway
Ma, L., Li, J., Yu, W., Li, R., & Si, L. (2026) · Molecular and Cellular Biochemistry · doi:10.1007/s11010-026-05535-9
Dissecting the impact of SHC-1 inhibitors in enhancing the plasma membrane abundance of the CFTR channel across epithelial cell models
Barros, P., Pereira, M., Tomilov, A. A., Cortopassi, G. A., Jordan, P., & Matos, P. (2026) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2026.153757
Targeting histamine H4 receptor improves anti-tumoral response in a murine model of breast cancer
Vázquez, R., Saibene, P., Boix, M. E., Maio, M., Salamone, G. V., Balboa, L., & Vermeulen, M. E. (2026) · Frontiers in Immunology · doi:10.3389/fimmu.2026.1770957
“The MAPK ERK1/2 was associated with proliferation and migration in BC tumor cell lines (35); however, studies analyzing p-ERK levels in patient biopsies (36) yielded contradictory results.”
Radiogenomic landscape of the hallmarks of cancer
Zhang, G., Guo, Y., Yang, Y., Li, T., Gong, B., Lou, J., Li, Y., Peng, S., Liu, C., Yuan, X., et al. (2026) · Biomarker Research · doi:10.1186/s40364-026-00920-4
“Therefore, BRAF is considered an important oncogenic driver gene [90–92].”
Efficacy of oncolytic viruses (OVs) in malignant tumor therapy: a review on its therapeutic aspects
Das, S., Goswami, H. R., Barman, I., & Talukdar, N. (2026) · Clinica Chimica Acta · doi:10.1016/j.cca.2026.121017 · Cited by 1
GAB3 suppresses lung adenocarcinoma progression by inhibiting the MAPK signaling and potentiating CD8+ T cell immunity
Wang, D., Xiao, C., Fan, T., Deng, Z., Yin, H., Liu, Y., Li, J., Ji, Y., Cai, W., Liao, T., et al. (2026) · Cancer Letters · doi:10.1016/j.canlet.2026.218532
T-LAK cell-originated protein kinase promotes tumorigenesis and metastasis of pancreatic neuroendocrine neoplasms via mitogen-activated protein kinase axis activation
Meng, M., Chen, Q., Yuan, M., Guo, X., Ren, S.-Q., & Yuan, C.-H. (2026) · World Journal of Gastrointestinal Surgery · doi:10.4240/wjgs.v18.i4.115798
Progressive IL-13 signaling promotes inflammation-associated liver fibrosis via IL-13RA2/MEK/ERK activation in Schistosoma japonicum infection
Xiong, R., Du, J., Yang, Y., Zhu, Y., Ni, Y., Chen, L., Hou, M., Xu, Z., Chen, L., & Ji, M. (2026) · Journal of Biomedical Research · doi:10.7555/jbr.39.20250475
Structurally diverse sesquiterpenoid glucoside esters from Cissampelopsis volubilis suppress triple-negative breast cancer via RAS-ERK signaling axis
Yan, Y., Wang, Y., Zhang, X., Ao, J., Zhang, Z., Wang, N., Hao, X., Ning, F., Zhang, L., & Tang, L. (2026) · Bioorganic Chemistry · doi:10.1016/j.bioorg.2026.109917
Proteomic approaches for interrogating kinase signaling networks
Berryhill, C. A., East, M. P., Hanquier, J. N., Johnson, G. L., & Angus, S. P. (2026) · Journal of Investigative Dermatology · doi:10.1016/j.jid.2026.03.032
Characterization of Chromosomal Translocations in Canine Solid Tumor Genomes
Kim, S., Woo, S.-W., Bae, H., Jeon, Y., Yu, D., & Kim, J. (2026) · Journal of Agriculture & Life Science · doi:10.14397/jals.2026.60.1.113
Advances in MAPK pathway-targeted therapy for ameloblastoma: A literature review.
Lv, Y., Yang, Z., Pan, Z.-Y., Liu, X.-W., Yu, J., Li, B.-S., & Zhang, F.-H. (2026) · Journal of Stomatology Oral and Maxillofacial Surgery · doi:10.1016/j.jormas.2026.102829
IGF2BP2 Promotes Oral Squamous Cell Carcinoma Progression and Is Associated with MAPK Signaling and Macrophage-Related Immune Features
Li, J. S., Yue, G., Zhao, M., Yan, F., Zhang, H., Xiong, H., Li, M., & Liu, B. (2026) · ACS Omega · doi:10.1021/acsomega.5c11808
The microbiome-inflammation-immune axis in oral squamous cell carcinoma: from mechanistic insights to therapeutic perspectives
Wang, Z., Bian, Q., Chu, Y., Zhu, W. J., Qin, Y., & Zheng, J. (2026) · Frontiers in Immunology · doi:10.3389/fimmu.2026.1842459 · Cited by 1
“These include organismal development, cell cycle control, proliferation and differentiation, survival, and cell death (51, 52).”
ERK autoinhibition mechanism informs a drug combination strategy
Regev, C., Jang, H., & Nussinov, R. (2026) · Protein Science · doi:10.1002/pro.70650
“This activation influences gene expression and cellular growth, underscoring their significance in both normal cellular processes and pathological conditions (Maik-Rachline et al., 2019; Ram et al., 2023; Seger, 2024; Sugiura et al., 2021; Ullah et al., 2022).”

Authors: Ullah, R., Yin, Q., Snell, A. H., & Wan, L.
Affiliations: Moffitt Cancer Center (US)
Corresponding author: Wan, Lixin
ORCID: Yin, Qing
Snell, Aidan H.
Wan, Lixin
Venue: Seminars in Cancer Biology
Publisher: Elsevier BV
Published: 2022-10
Volume: 85
Pages: 123-154
ISSN: 1044-579X (ISSN-L)
DOI: 10.1016/j.semcancer.2021.05.010
OpenAlex: W3160873367
Cited by: 553
References: 506
Citations by year: 2026: 123 · 2025: 164 · 2024: 173 · 2023: 69 · 2022: 19
FWCI: 7.08
Type: journal article
Language: en
Open access: closed
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)
doi.org/10.15223/policy-017 (stm-asf)
doi.org/10.15223/policy-037 (stm-asf)
doi.org/10.15223/policy-012 (stm-asf)
doi.org/10.15223/policy-029 (stm-asf)
doi.org/10.15223/policy-004 (stm-asf)
Locations: Seminars in Cancer Biology (publishedVersion)
PubMed (publishedVersion)
Funders: Melanoma Research Alliance
Florida Department of Health
American Cancer Society
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Melanoma and MAPK Pathways
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Tyrosine Phosphatases
Keywords: Raf/MEK/ERK pathway, MAPK signaling, BRAF V600E mutation, Raf isoforms, MEK1/2, ERK1/2, Ras activation, receptor tyrosine kinase signaling, tumor evolution, cancer therapy, small molecule inhibitors, signaling crosstalk, oncogenic mutations
MeSH terms: Humans, Neoplasms, Signal Transduction, Mitogen-Activated Protein Kinase Kinases, MAP Kinase Signaling System, Extracellular Signal-Regulated MAP Kinases, Proto-Oncogene Proteins B-raf

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

RAF-MEK-ERK pathway in cancer evolution and treatment

Abstract

Overview

Integrity signals

Verification

Claims the paper makes

Claims other papers make about this one

Citations

Cites

Cited by

Related

Metadata

Record

About these checks