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REVIEW

After a Decade of Therapy Revolution in Cutaneous Melanoma—Perspectives on Emerging Treatment Strategies

Sebastian A. Wohlfeil1,2,3,*, Jochen S. Utikal1,2,3
1 Skin Cancer Unit, German Cancer Research Center (DKFZ), Heidelberg, Germany
2 Department of Dermatology, Venereology and Allergology, University Medical Center Mannheim, Ruprecht-Karl University of Heidelberg, Mannheim, Germany
3 DKFZ Hector Cancer Institute, University Medical Center Mannheim, Mannheim, Germany
* Corresponding Author: Sebastian A. Wohlfeil. Email: email

Oncology Research https://doi.org/10.32604/or.2026.078650

Received 05 January 2026; Accepted 03 March 2026; Published online 16 March 2026

Abstract

Over the past decade, the therapeutic paradigm of cutaneous melanoma has been transformed strongly, driven by advances in immuno-oncology and precision medicine. Building on the success of immune checkpoint blockade and targeted therapy, new treatment strategies now aim to improve efficacy, overcome resistance, and prolong the durability of responses. Clinical trials on neoadjuvant therapy supporting its clinical use are presented. Furthermore, the latest progress in combinatorial immune checkpoint inhibition such as dual anti-LAG-3 or anti-TIGIT with anti-PD-1 blockade, next-generation bispecific antibody development, mRNA-based vaccines in clinical practice, and intralesional therapies are summarized. Additionally, it outlines the growing significance of novel cellular approaches, such as adoptive cell therapy with tumor-infiltrating lymphocytes (TILs) or engineered T cells. By integrating insights from recent clinical and translational research, the review highlights promising therapeutic avenues and with treatment sequencing and biomarker research, it outlines key challenges for future melanoma management. This review aims to summarize selected ongoing clinical studies and outline prospective directions in systemic melanoma therapy.

Keywords

Melanoma; immune checkpoint inhibition; neoadjuvant therapy; cancer vaccines; bispecific antibodies

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