Advanced Acral Melanoma Therapies: Current Status and Future Directions
Related Experiment Video
Updated: Aug 28, 2025
A 3D Organotypic Melanoma Spheroid Skin Model
Published on: May 18, 2018
Yiqun Zhang1, Shijie Lan1, Di Wu2
1Cancer Center, The First Hospital of Jilin University, 1 Xinmin St, Changchun, 130021, China.
Opinion Statement:
Melanoma is one of the deadliest malignancies. Its incidence has been significantly increasing in most countries in recent decades. Acral melanoma (AM), a peculiar subgroup of melanoma occurring on the palms, soles, and nails, is the main subtype of melanoma in people of color and is extremely rare in Caucasians. Although great progress has been made in melanoma treatment in recent years, patients with AM have shown limited benefit from current therapies and thus consequently have worse overall survival rates. Achieving durable therapeutic responses in this high-risk melanoma subtype represents one of the greatest challenges in the field. The frequency of BRAF mutations in AM is much lower than that in cutaneous melanoma, which prevents most AM patients from receiving treatment with BRAF inhibitors. However, AM has more frequent mutations such as KIT and CDK4/6, so targeted therapy may still improve the survival of some AM patients in the future. AM may be less susceptible to immune checkpoint inhibitors because of the poor immunogenicity. Therefore, how to enhance the immune response to the tumor cells may be the key to the application of immune checkpoint inhibitors in advanced AM. Anti-angiogenic drugs, albumin paclitaxel, or interferons are thought to enhance the effectiveness of immune checkpoint inhibitors. Combination therapies based on the backbone of PD-1 are more likely to provide greater clinical benefits. Understanding the molecular landscapes and immune microenvironment of AM will help optimize our combinatory strategies.
Insights
Acral melanoma (AM) is a rare, aggressive skin cancer with poor treatment outcomes. Future therapies may involve targeting KIT/CDK4/6 mutations and enhancing immune responses for better survival.
Area of Science:
- Oncology
- Dermatology
- Cancer Research
Background:
- Acral melanoma (AM) is an aggressive skin cancer subtype with increasing incidence, particularly in people of color.
- AM presents unique challenges due to lower BRAF mutation frequency and limited response to current therapies, leading to poorer survival rates.
- Durable therapeutic responses in AM remain a significant challenge in clinical oncology.
Purpose of the Study:
- To review the current understanding of acral melanoma (AM) molecular landscape and immune microenvironment.
- To explore potential targeted therapy and immunotherapy strategies for advanced AM.
- To identify optimal combinatory therapeutic approaches for improving AM patient outcomes.
Main Methods:
- Review of existing literature on acral melanoma (AM) genetics, immunology, and treatment responses.
- Analysis of mutation frequencies (BRAF, KIT, CDK4/6) in AM compared to cutaneous melanoma.
- Evaluation of the potential of immune checkpoint inhibitors and combination therapies.
Main Results:
- Acral melanoma (AM) exhibits lower BRAF mutation rates but higher frequencies of KIT and CDK4/6 mutations compared to cutaneous melanoma.
- AM may be less responsive to immune checkpoint inhibitors due to poor immunogenicity.
- Combination therapies, potentially involving anti-angiogenic drugs, albumin paclitaxel, or interferons with PD-1 inhibitors, show promise.
Conclusions:
- Targeted therapies focusing on KIT and CDK4/6 mutations offer future treatment avenues for AM.
- Enhancing anti-tumor immune responses is crucial for the efficacy of immune checkpoint inhibitors in advanced AM.
- Understanding AM's molecular and immune characteristics is key to developing effective combination strategies and improving patient survival.
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