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Simultaneous blocking of the pan-RAF and S100B pathways as a synergistic therapeutic strategy against malignant melanoma
Wu,Ke Jia1; Ho,Shih Hsin2; Wu,Chun3; Wang,Hui Min D.4,5,6; Ma,Dik Lung3; Leung,Chung Hang1
2021-02-01
Source PublicationJournal of Cellular and Molecular Medicine
ISSN1582-1838
Volume25Issue:4Pages:1972-1981
Abstract

Melanoma is a very aggressive form of skin cancer. Although BRAF inhibitors have been utilized for melanoma therapy, advanced melanoma patients still face a low five-year survival rate. Recent studies have shown that CRAF can compensate for BRAF depletion via regulating DNA synthesis to remain melanoma proliferation. Hence, targeting CRAF either alone or in combination with other protein pathways is a potential avenue for melanoma therapy. Based on our previously reported CRAF-selective inhibitor for renal cancer therapy, we have herein discovered an analogue (complex 1) from the reported CRAF library suppresses melanoma cell proliferation and melanoma tumour growth in murine models of melanoma via blocking the S100B and RAF pathways. Intriguingly, we discovered that inhibiting BRAF together with S100B exerts a novel synergistic effect to significantly restore p53 transcription activity and inhibit melanoma cell proliferation, whereas blocking BRAF together with CRAF only had an additive effect. We envision that blocking the pan-RAF and S100B/p53 pathways might be a novel synergistic strategy for melanoma therapy and that complex 1 is a potential inhibitor against melanoma via blocking the pan-RAF and S100B pathways.

KeywordDrug Discovery Malignant Melanoma Pan-raf S100b-p53 Interaction Synergistic
DOI10.1111/jcmm.15994
URLView the original
Indexed BySCIE
Language英語English
WOS Research AreaCell Biology ; Research & Experimental Medicine
WOS SubjectCell Biology ; Medicine, Research & Experimental
WOS IDWOS:000603419700001
Scopus ID2-s2.0-85098259109
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Cited Times [WOS]:1   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionUniversity of Macau
Corresponding AuthorWang,Hui Min D.; Ma,Dik Lung; Leung,Chung Hang
Affiliation1.State Key Laboratory of Quality Research in Chinese Medicine,Institute of Chinese Medical Sciences,University of Macau,Macao
2.State Key Laboratory of Urban Water Resource and Environment,School of Environment,Harbin Institute of Technology,Harbin,China
3.Department of Chemistry,Hong Kong Baptist University,Kowloon Tong,Hong Kong
4.Graduate Institute of Biomedical Engineering National Chung Hsing University,Taichung,Taiwan
5.Graduate Institute of Medicine,College of Medicine,Kaohsiung Medical University,Kaohsiung,Taiwan
6.Department of Medical Laboratory Science and Biotechnology,China Medical University,Taichung City,Taiwan
First Author AffilicationInstitute of Chinese Medical Sciences
Corresponding Author AffilicationInstitute of Chinese Medical Sciences
Recommended Citation
GB/T 7714
Wu,Ke Jia,Ho,Shih Hsin,Wu,Chun,et al. Simultaneous blocking of the pan-RAF and S100B pathways as a synergistic therapeutic strategy against malignant melanoma[J]. Journal of Cellular and Molecular Medicine,2021,25(4):1972-1981.
APA Wu,Ke Jia,Ho,Shih Hsin,Wu,Chun,Wang,Hui Min D.,Ma,Dik Lung,&Leung,Chung Hang.(2021).Simultaneous blocking of the pan-RAF and S100B pathways as a synergistic therapeutic strategy against malignant melanoma.Journal of Cellular and Molecular Medicine,25(4),1972-1981.
MLA Wu,Ke Jia,et al."Simultaneous blocking of the pan-RAF and S100B pathways as a synergistic therapeutic strategy against malignant melanoma".Journal of Cellular and Molecular Medicine 25.4(2021):1972-1981.
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