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Selumetinib: a selective MEK1 inhibitor for solid tumor treatment

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Abstract

Cancer incidence is rapidly growing. Solid tumors are responsible for a majority of cancers. Recently, molecular-targeted agents have played a significant role in cancer treatment. Ras–Raf–MEK–ERK signaling pathway, is a substantial element in the survival, propagation, and drug resistance of human cancers. MEK is a specific part of the so-called cascade, and ERK proteins are its sole target. Furthermore, their downstream position in the Ras–ERK cascade, is noteworthy to direct their function in patients with upstream mutated genes. MEK1 mutations are responsible for initiating several solid tumors. Selumetinib (AZD6244) is a second-generation, selective, potent, and non-ATP competitive allosteric MEK1 inhibitor. The efficacy of selumetinib in various solid tumors such as colorectal cancer, lung cancer, neurofibroma, and melanoma is investigated. The present paper provides an overview of the MAPK cascade, the role of selumetinib as a MEK1/2 inhibitor, and the related findings of clinical trials for solid tumor treatment.

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Abbreviations

AKT:

Protein kinase B

BC:

Biliary tract cancer

ERα:

Estrogen receptor alpha

HCC:

Hepatocellular carcinoma

MEKi:

Mitogen-activated protein kinase inhibitor

NSCLC:

Non-small-cell lung cancer

PI3K:

Phosphoinositide 3-kinase

TSH:

Thyroid-stimulating hormone

US:

United States

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Funding

No funding was received for conducting this study.

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Authors and Affiliations

  1. Student Research Committee, Urmia University of Medical Sciences, Urmia, Iran

    Mohaddeseh Hedayat

  2. Cellular and Molecular Research Center, Cellular and Molecular Medicine Institute, Urmia University of Medical Sciences, Urmia, Iran

    Reza Jafari

  3. Department of Immunology and Genetics, School of Medicine, Urmia University of Medical Sciences, Urmia, Iran

    Reza Jafari

  4. Experimental and Applied Pharmaceutical Sciences Research Center, Urmia University of Medical Sciences, Urmia, Iran

    Naime Majidi Zolbanin

  5. Department of Pharmacology and Toxicology, School of Pharmacy, Urmia University of Medical Sciences, Urmia, Iran

    Naime Majidi Zolbanin

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  1. Mohaddeseh Hedayat
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  2. Reza Jafari
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  3. Naime Majidi Zolbanin
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R J and N M Z were involved in conception and manuscript design and made important revisions and confirmed final revision. M H, R J, and N M Z were involved in collection of data and manuscript writing. All authors reviewed and approved the final version of the manuscript.

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Correspondence to Naime Majidi Zolbanin.

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Hedayat, M., Jafari, R. & Majidi Zolbanin, N. Selumetinib: a selective MEK1 inhibitor for solid tumor treatment. Clin Exp Med 23, 229–244 (2023). https://doi.org/10.1007/s10238-021-00783-z

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  • DOI: https://doi.org/10.1007/s10238-021-00783-z

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