Cited by 212Melanoma and MAPK PathwaysProtein Kinase Regulation and GTPase SignalingProtein Tyrosine Phosphatases

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

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Song, Yanlin, Bi, Zhenfei, Liu, Yu, Qin, Furong, Wei, Yuquan, Wei, Xiawei·2023·Genes & Diseases

DOI 10.1016/j.gendis.2022.05.006PMC PMC10066287

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Abstract

Molecular target inhibitors have been regularly approved by Food and Drug Administration (FDA) for tumor treatment, and most of them intervene in tumor cell proliferation and metabolism. The RAS-RAF-MEK-ERK pathway is a conserved signaling pathway that plays vital roles in cell proliferation, survival, and differentiation. The aberrant activation of the RAS-RAF-MEK-ERK signaling pathway induces tumors. About 33% of tumors harbor RAS mutations, while 8% of tumors are driven by RAF mutations. Great efforts have been dedicated to targeting the signaling pathway for cancer treatment in the past decades. In this review, we summarized the development of inhibitors targeting the RAS-RAF-MEK-ERK pathway with an emphasis on those used in clinical treatment. Moreover, we discussed the potential combinations of inhibitors that target the RAS-RAF-MEK-ERK signaling pathway and other signaling pathways. The inhibitors targeting the RAS-RAF-MEK-ERK pathway have essentially modified the therapeutic strategy against various cancers and deserve more attention in the current cancer research and treatment.

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Authors: Song, Y., Bi, Z., Liu, Y., Qin, F., Wei, Y., & Wei, X.
Affiliations: Sichuan University (CN)
Corresponding author: Wei, Xiawei
ORCID: Song, Yanlin
Bi, Zhenfei
Liu, Yu
Wei, Yuquan
Wei, Xiawei
Venue: Genes & Diseases
Publisher: Elsevier BV
Published: 2023-01
Volume: 10
Issue: 1
Pages: 76-88
ISSN: 2352-3042 (ISSN-L)
DOI: 10.1016/j.gendis.2022.05.006
PMC: PMC10066287
OpenAlex: W4280552157
Cited by: 212
References: 206
Citations by year: 2026: 52 · 2025: 77 · 2024: 58 · 2023: 23
FWCI: 4.17
Type: journal article
Language: en
Open access: gold
doi.org
Licence: cc-by-nc-nd
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)
creativecommons.org/licenses/by-nc-nd/4.0/ (vor)
Locations: Genes & Diseases (publishedVersion, cc-by-nc-nd)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders: National Outstanding Youth Science Fund Project of National Natural Science Foundation of China (32122052)
Key Research and Development Program of Sichuan Province (2020YFS0553)
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: RAS/MAPK pathway, targeted cancer therapy, RAS inhibitors, RAF inhibitors, MEK inhibitors, ERK inhibitor, combination therapy, RAS mutations, RAF mutations, clinical trials, tumor cell proliferation

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

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