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
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.
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“Activated RAS proteins can interact with many downstream effector proteins, such as RAF kinase, son of sevenless (SOS), phosphatidylinositol 3-kinase (PI3K) and Ral guanine nucleotide dissociation stimulating factors (RalGDS), which regulate cell events such as cell proliferation and apoptosis.323–325”
From Recent advances in targeting the “undruggable” proteins: from drug discovery to clinical trials (2023) · cites this paper as [325]
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Recent advances in targeting the “undruggable” proteins: from drug discovery to clinical trials
Xie, X., Yu, T., Li, X., Zhang, N., Foster, L. J., Peng, C., Huang, W., & He, G. (2023) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-023-01589-z · Cited by 396
Hepatocellular carcinoma: signaling pathways and therapeutic advances
Zheng, J., Wang, S., Xia, L., Sun, Z., Chan, K. M., Bernards, R., Qin, W., Chen, J., Xia, Q., & Jin, H. (2025) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-024-02075-w · Cited by 421
Therapeutic advances of targeting receptor tyrosine kinases in cancer
Tomuleasa, C., Tigu, A.-B., Munteanu, R. A., Moldovan, C. S., Kegyes, D., Onaciu, A., Gulei, D., Ghiaur, G., Einsele, H., & Croce, C. M. (2024) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-024-01899-w · Cited by 307
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The molecular mechanism and therapeutic landscape of copper and cuproptosis in cancer
Guo, Z., Chen, D., Yao, L., Sun, Y., Li, D., Le, J., Dian, Y., Zeng, F., Chen, X., & Deng, G. (2025) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-025-02192-0 · Cited by 221
“115,116 119 This copper-dependent vulnerability has been demonstrated in tumor models with BRAF or KRAS mutations.”
Metadata
- Authors
- Ullah, R., Yin, Q., Snell, A. H., & Wan, L.
- Affiliations
- Moffitt Cancer Center (US)
- Corresponding author
- Wan, Lixin
- Venue
- Seminars in Cancer Biology
- Publisher
- Elsevier BV
- Published
- 2022-10
- Volume
- 85
- Pages
- 123-154
- ISSN
- 1044-579X (ISSN-L)
- 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
- 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
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