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Clinical Advances in the Management of Melanoma

A special issue of Journal of Clinical Medicine (ISSN 2077-0383). This special issue belongs to the section "Dermatology".

Deadline for manuscript submissions: 15 April 2026 | Viewed by 828

Special Issue Editors


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Guest Editor
Division of Surgical Oncology, Department of Surgery, City of Hope National Medical Center, Duarte, CA 91010, USA
Interests: melanoma; surgical oncology; immuno-oncology
Department of Medical Oncology and Therapeutics Research, City of Hope, Duarte, CA 91010, USA
Interests: melanoma; surgical oncology; immuno-oncology

Special Issue Information

Dear Colleagues,

Melanoma management has undergone transformative clinical advances in recent years, driven by breakthroughs in targeted therapies and immunomodulation. This review highlights key innovations shaping contemporary treatment paradigms, including BRAF/MEK inhibitors for mutation-specific targeting, immune checkpoint inhibitors such as anti-PD-1/CTLA-4, and TIL adoptive cell therapy that have improved survival in advanced disease. As our understanding of the underlying genomic alterations that drive melanoma improves, there is increased interest in tailoring therapy regimens based on histologic and molecular subtypes. Emerging approaches such as oncolytic viruses, cancer vaccines, bispecific T-cell Engagers (BiTEs), bispecific antibodies, and combination regimens are discussed, with attention to their real-world efficacy and safety profiles. Additionally, we address challenges in treatment sequencing, the clinical utility of adjuvant and neoadjuvant strategies for stage III/IV resectable melanoma, resistance mechanisms, and biomarker and liquid-biopsy development to guide personalized decision-making. The integration of these innovations into multidisciplinary care models underscores the importance of tailored therapies in optimizing patient outcomes. By synthesizing recent trial data and expert consensus, this work provides a practical framework for clinicians navigating the rapidly evolving landscape of melanoma therapeutics.

Dr. Kelly M. Mahuron
Dr. Yan Xing
Guest Editors

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Keywords

  • melanoma immunotherapy
  • targeted therapy
  • immune checkpoint inhibitors
  • melanoma subtypes
  • adjuvant treatment
  • neoadjuvant treatment
  • tumor-infiltrating lymphocytes (TILs) therapy
  • combination therapy
  • molecular profiling
  • bi-omarker-driven therapy
  • clinical decision-making
  • liquid biopsy

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Published Papers (1 paper)

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Review

34 pages, 1572 KB  
Review
Pathway-Specific Therapeutic Modulation of Melanoma: Small-Molecule Inhibition of BRAF–MEK and KIT Signaling in Contemporary Precision Oncology with a Special Focus on Vemurafenib, Trametinib, and Imatinib
by Piotr Kawczak and Tomasz Bączek
J. Clin. Med. 2025, 14(22), 7906; https://doi.org/10.3390/jcm14227906 - 7 Nov 2025
Viewed by 731
Abstract
Melanoma is an aggressive form of skin cancer marked by unique genetic alterations that promote tumor growth and resistance to therapy. Advances in targeted therapy have markedly improved clinical outcomes by selectively inhibiting key oncogenic pathways. This review focuses on three clinically relevant [...] Read more.
Melanoma is an aggressive form of skin cancer marked by unique genetic alterations that promote tumor growth and resistance to therapy. Advances in targeted therapy have markedly improved clinical outcomes by selectively inhibiting key oncogenic pathways. This review focuses on three clinically relevant agents—vemurafenib, trametinib, and imatinib—analyzing their mechanisms of action, clinical applications, efficacy, and limitations. Vemurafenib, a selective BRAFV600E inhibitor, significantly extends progression-free and overall survival in BRAF-mutant melanoma but is limited by acquired resistance and frequent cutaneous toxicities. Trametinib, a MEK1/2 inhibitor, acts downstream in the MAPK pathway and is typically combined with BRAF inhibitors to enhance efficacy and delay resistance. Imatinib, targeting c-KIT and PDGFR mutations, demonstrates therapeutic benefit primarily in acral and mucosal melanoma subtypes, though with lower response rates than BRAF-directed therapies. Adverse events associated with these drugs are generally manageable with appropriate monitoring. Despite substantial advances, secondary mutations and reactivation of oncogenic signaling remain major challenges. This narrative review integrates data from clinical, preclinical, and real-world studies to update the current understanding of targeted therapies in cutaneous melanoma and highlight ongoing research aimed at overcoming resistance and optimizing personalized treatment strategies. Full article
(This article belongs to the Special Issue Clinical Advances in the Management of Melanoma)
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