Rather RA. Oncogenic B-Raf proto-oncogene, serine/threonine kinase-mediated hedgehog signalling in the pathogenesis and targeted therapy of melanoma. World J Clin Oncol 2025; 16(10): 105117 [DOI: 10.5306/wjco.v16.i10.105117]
Corresponding Author of This Article
Rafiq A Rather, PhD, Assistant Professor, Department of Clinical Biochemistry, Govt. Degree College Shopian, Gagren, Shopian 192303, Jammu and Kashmir, India. rafiqahmad11@gmail.com
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Biochemistry & Molecular Biology
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This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Oct 24, 2025 (publication date) through Oct 27, 2025
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World Journal of Clinical Oncology
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2218-4333
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Baishideng Publishing Group Inc, 7041 Koll Center Parkway, Suite 160, Pleasanton, CA 94566, USA
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Rather RA. Oncogenic B-Raf proto-oncogene, serine/threonine kinase-mediated hedgehog signalling in the pathogenesis and targeted therapy of melanoma. World J Clin Oncol 2025; 16(10): 105117 [DOI: 10.5306/wjco.v16.i10.105117]
World J Clin Oncol. Oct 24, 2025; 16(10): 105117 Published online Oct 24, 2025. doi: 10.5306/wjco.v16.i10.105117
Oncogenic B-Raf proto-oncogene, serine/threonine kinase-mediated hedgehog signalling in the pathogenesis and targeted therapy of melanoma
Rafiq A Rather
Rafiq A Rather, Department of Clinical Biochemistry, Govt. Degree College Shopian, Shopian 192303, Jammu and Kashmir, India
Author contributions: Rather RA conceived the idea and wrote the manuscript.
Supported by the Science and Engineering Research Board, No. PDF/2016/002730.
Conflict-of-interest statement: The author reports no relevant conflicts of interest for this article.
Open Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Rafiq A Rather, PhD, Assistant Professor, Department of Clinical Biochemistry, Govt. Degree College Shopian, Gagren, Shopian 192303, Jammu and Kashmir, India. rafiqahmad11@gmail.com
Received: January 13, 2025 Revised: May 26, 2025 Accepted: September 3, 2025 Published online: October 24, 2025 Processing time: 285 Days and 17.5 Hours
Core Tip
Core Tip: Oncogenic B-Raf proto-oncogene, serine/threonine kinase activates the hedgehog signaling pathway, triggering glioma-associated oncogene homolog (GLI) 1/2 transcription factors that promote melanoma cell invasion and sustain cancer stem cell self-renewal, contributing to the malignancy’s therapeutic resistance. Histone deacetylases 1/2 (HDAC1/2) suppress the acetylation of GLI1/2, facilitating their activation. Inhibiting HDAC1/2 may stabilize GLI proteins in their inactive, acetylated form, offering a novel approach to inhibit melanoma progression. Hedgehog signaling induces HDAC1/2 expression, creating a feedback loop that amplifies GLI-mediated transcription, promoting cancer stem cell renewal. Disrupting this loop could unveil new therapeutic avenues for overcoming melanoma’s resistance to treatment.
