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Updated: Feb 20, 2026
A 3D Organotypic Melanoma Spheroid Skin Model
Published on: May 18, 2018
New Drug Combination Strategies in Melanoma: Current Status and Future Directions
Ahmad Najem1, Mohammad Krayem1, Anne Perdrix1,2
1Laboratory of Oncology and Experimental Surgery Institute Jules Bordet, Université Libre de Bruxelles, Brussels, Belgium.
Abstract:
Melanoma is the deadliest form of skin cancer and one of the most difficult cancers to treat. Overall, melanomas have more mutations than any other cancer type. Oncogenic mutations in c-KIT, NRAS and BRAF components of the MAPK pathway have been identified in nearly 90% of cutaneous melanoma and this information has been used to develop small molecules that inhibit their activity. Highly selective BRAF and MEK inhibitors have demonstrated impressive clinical results. However, the short duration of response, the acquired resistance in most cases and the toxicity issues support the rationale for drug combination approaches to improve the outcome of MAPK inhibitors, increase their efficacy, prevent and/or overcome resistance. This review discusses several promising rational combinatorial strategies investigated or could be investigated in clinical studies.
Insights
This review explores combining MAPK inhibitors to improve melanoma treatment outcomes. Strategies aim to increase efficacy and overcome resistance in this deadly skin cancer.
Area of Science:
- Oncology
- Dermatology
- Cancer Genetics
Background:
- Melanoma is a deadly skin cancer with a high mutation rate.
- Mutations in BRAF, NRAS, and c-KIT within the MAPK pathway are common in melanoma.
- Targeted therapies like BRAF and MEK inhibitors show promise but face challenges.
Purpose of the Study:
- To review rational drug combination strategies for MAPK inhibitors in melanoma.
- To discuss approaches to improve efficacy and overcome resistance to targeted therapies.
Main Methods:
- Review of existing and potential clinical studies on drug combinations.
- Analysis of MAPK pathway mutations and resistance mechanisms in melanoma.
Main Results:
- BRAF and MEK inhibitors have shown clinical efficacy.
- Acquired resistance and toxicity limit the long-term effectiveness of single-agent therapies.
- Combinatorial approaches are being investigated to enhance treatment outcomes.
Conclusions:
- Drug combinations are crucial for improving melanoma treatment efficacy.
- Targeted strategies aim to prevent or overcome resistance to MAPK inhibitors.
- Further clinical investigation of combinatorial approaches is warranted.
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