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Updated: Jul 25, 2025
A 3D Organotypic Melanoma Spheroid Skin Model
Published on: May 18, 2018
New Approaches to Targeted Therapy in Melanoma
Manuel Felipe Fernandez1, Jacob Choi1, Jeffrey Sosman1
1Robert H. Lurie Comprehensive Cancer Center, Division of Hematology/Oncology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA.
Abstract:
It was just slightly more than a decade ago when metastatic melanoma carried a dismal prognosis with few, if any, effective therapies. Since then, the evolution of cancer immunotherapy has led to new and effective treatment approaches for melanoma. However, despite these advances, a sizable portion of patients with advanced melanoma have de novo or acquired resistance to immune checkpoint inhibitors. At the same time, therapies (BRAF plus MEK inhibitors) targeting the BRAF mutations found in 40-50% of cutaneous melanomas have also been critical for optimizing management and improving patient outcomes. Even though immunotherapy has been established as the initial therapy in most patients with cutaneous melanoma, subsequent effective therapy is limited to BRAF melanoma. For all other melanoma patients, driver mutations have not been effectively targeted. Numerous efforts are underway to target melanomas with NRAS mutations, NF-1 LOF mutations, and other genetic alterations leading to activation of the MAP kinase pathway. In this era of personalized medicine, we will review the current genetic landscape, molecular classifications, emerging drug targets, and the potential for combination therapies for non-BRAF melanoma.
Insights
Advances in cancer immunotherapy have improved melanoma treatment, but resistance remains a challenge. Research is exploring targeted therapies for non-BRAF mutations to improve outcomes for more melanoma patients.
Area of Science:
- Oncology
- Dermatology
- Genetics
Background:
- Metastatic melanoma historically had a poor prognosis with limited effective treatments.
- Cancer immunotherapy has revolutionized melanoma treatment, offering new therapeutic avenues.
- Despite advances, many patients develop resistance to immune checkpoint inhibitors, and targeted therapies are limited to BRAF-mutated melanomas.
Purpose of the Study:
- To review the current genetic landscape of non-BRAF melanoma.
- To discuss molecular classifications and emerging drug targets for non-BRAF melanoma.
- To explore the potential of combination therapies for non-BRAF melanoma.
Main Methods:
- Review of current literature on melanoma genetics and targeted therapies.
- Analysis of molecular classifications and driver mutations in non-BRAF melanoma.
- Examination of emerging drug targets and combination therapy strategies.
Main Results:
- Immune checkpoint inhibitors are effective but face resistance in a significant patient subset.
- BRAF and MEK inhibitors offer improved outcomes for patients with BRAF mutations.
- Effective targeted therapies for non-BRAF melanoma, including NRAS and NF-1 mutations, are under development.
Conclusions:
- Personalized medicine approaches are crucial for optimizing melanoma treatment.
- Targeting genetic alterations beyond BRAF mutations is essential for improving outcomes in a broader patient population.
- Combination therapies hold promise for overcoming resistance and enhancing treatment efficacy in non-BRAF melanoma.
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