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Updated: Nov 16, 2025
A 3D Organotypic Melanoma Spheroid Skin Model
Published on: May 18, 2018
Decoding Melanoma Development and Progression: Identification of Therapeutic Vulnerabilities
Kevinn Eddy1,2, Raj Shah2,3, Suzie Chen1,2,4,5
1Graduate Program in Cellular and Molecular Pharmacology, School of Graduate Studies, Rutgers University, Piscataway, NJ, United States.
Abstract:
Melanoma, a cancer of the skin, arises from transformed melanocytes. Melanoma has the highest mutational burden of any cancer partially attributed to UV induced DNA damage. Localized melanoma is "curable" by surgical resection and is followed by radiation therapy to eliminate any remaining cancer cells. Targeted therapies against components of the MAPK signaling cascade and immunotherapies which block immune checkpoints have shown remarkable clinical responses, however with the onset of resistance in most patients, and, disease relapse, these patients eventually become refractory to treatments. Although great advances have been made in our understanding of the metastatic process in cancers including melanoma, therapy failure suggests that much remains to be learned and understood about the multi-step process of tumor metastasis. In this review we provide an overview of melanocytic transformation into malignant melanoma and key molecular events that occur during this evolution. A better understanding of the complex processes entailing cancer cell dissemination will improve the mechanistic driven design of therapies that target specific steps involved in cancer metastasis to improve clinical response rates and overall survival in all cancer patients.
Insights
This review details melanoma development from melanocytes and highlights challenges in current treatments due to resistance and relapse. Understanding cancer cell metastasis is key to developing more effective melanoma therapies.
Area of Science:
- Oncology
- Dermatology
- Cancer Biology
Background:
- Melanoma, a skin cancer from melanocytes, has a high mutation rate, often due to UV DNA damage.
- Current treatments like targeted therapies and immunotherapies show initial success but often face resistance and relapse.
- Despite advances, understanding melanoma metastasis is crucial for improving patient outcomes.
Purpose of the Study:
- To provide an overview of melanoma development from melanocytes.
- To outline key molecular events in melanoma evolution and metastasis.
- To emphasize the need for better understanding of cancer cell dissemination for improved therapies.
Main Methods:
- Literature review of melanoma pathogenesis.
- Analysis of molecular events in melanocytic transformation.
- Discussion of therapeutic strategies and resistance mechanisms.
Main Results:
- Melanoma arises from transformed melanocytes with significant UV-induced DNA damage.
- Targeted and immune checkpoint therapies are effective but limited by resistance and relapse.
- Metastasis remains a complex process requiring further investigation.
Conclusions:
- A comprehensive understanding of melanoma metastasis is essential for designing novel, targeted therapies.
- Improving mechanistic insights into cancer cell dissemination can enhance treatment efficacy.
- Further research into melanoma progression and metastasis is vital for improving patient survival rates.
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