# The Emerging Melanoma Management: Historical Perspective to Future Directions

## TL;DR

This paper reviews the history and future of melanoma treatments, focusing on immune therapies and new strategies like CAR-T and PROTAC.

## Contribution

The paper provides a comprehensive overview of evolving melanoma therapies and highlights promising future directions.

## Key findings

- Immune checkpoint blockade therapy is the main focus of current melanoma research.
- CAR-T/CAR-NK, PROTAC, and extracellular vesicle-based therapies show potential for future treatment.
- Combination therapies and new immune checkpoint inhibitors are improving clinical outcomes.

## Abstract

Cutaneous melanoma accounts for the majority of skin cancer-caused deaths. Melanoma management plans have been evolving rapidly. Here, we summarise clinical biomarkers and approved treatment options for cutaneous melanoma to date. We have compared the pros and cons of the latest therapies in terms of clinical benefits and discussed future directions for emerging therapeutic strategies. In summary, immune checkpoint blockade therapy remains the main focus of current studies; new combinations of approved immune checkpoint blockades or the addition of novel immune checkpoint inhibitors are expected to continue improving clinical outcomes, although CAR-T/CAR-NK, PROTAC-based targeted therapies, and extracellular vesicle-based treatment options show significant potential.

Cutaneous melanoma is an aggressive form of cancer that accounts for approximately 80% of skin cancer-associated mortality. Treatment strategies for melanoma have been rapidly evolving over the past two decades. Clinical outcomes for advanced melanoma patients have improved with the use of immune checkpoint inhibitors and targeted therapies, including combination therapies. In this review, we primarily focus on the evolution of novel therapies for advanced melanoma patients, existing and emerging melanoma biomarkers, and the most up-to-date treatment recommendations. Furthermore, we summarise ongoing studies, clinical trials, and emerging therapeutic strategies. In this review, we will walk you through how cutaneous melanoma treatment strategies have evolved over the past 50 years. We will provide background on how those strategies were developed, how they function, their pros and cons, and their performance in terms of clinical benefits. Lastly, we will provide insights into potential therapies and research areas. In summary, improving the efficacy of immune checkpoint blockade remains the most promising approach for improving cutaneous melanoma management. However, strategies such as CAR-T/NK, PROTAC, or extracellular vesicle-based therapies are also worth further investigation.