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Molecular genetic and immunotherapeutic targets in metastatic melanoma
C Melis1, A Rogiers2, O Bechter2
1Department of Pathology, University Hospitals of Leuven, University of Leuven KUL, Herestraat 49, 3000, Leuven, Belgium.
Abstract:
In recent years, melanoma treatment has radically changed with the emergence of targeted therapies and immunotherapies. Both have led to improved survival for patients with advanced or unresectable melanoma. Targeted therapies with BRAF inhibitors in the lead use the presence of activating driver mutations to inhibit tumour growth. Forty to 60% of melanomas harbour BRAF mutations, which makes them susceptible to treatment with BRAF and/or MEK inhibitors. In parallel, the development of immunotherapeutic agents has also expanded. These agents stimulate the endogenous immune system of the patient to eradicate cancer cells. Immune checkpoint inhibitors targeting cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) and programmed death 1 (PD-1) resulted in durable responses in a subset of patients. An important issue with immunotherapy lies in the identification of patients who will benefit from treatment. In this review, we will discuss these recent developments in melanoma therapy and highlight the role of the pathologist in both types of treatment.
Insights
Recent advances in melanoma treatment include targeted therapies like BRAF inhibitors and immunotherapies such as immune checkpoint inhibitors, improving survival for advanced melanoma patients. Identifying patients who benefit from these treatments remains crucial.
Area of Science:
- Oncology
- Immunology
- Dermatology
Background:
- Melanoma treatment has significantly advanced with targeted therapies and immunotherapies.
- These treatments have improved survival rates for patients with advanced or unresectable melanoma.
Purpose of the Study:
- To review recent developments in melanoma targeted therapies and immunotherapies.
- To highlight the role of the pathologist in guiding these treatments.
Main Methods:
- Review of targeted therapies, focusing on BRAF inhibitors for BRAF-mutated melanomas.
- Review of immunotherapies, including immune checkpoint inhibitors (CTLA-4 and PD-1).
Main Results:
- BRAF inhibitors are effective in 40-60% of melanomas with BRAF mutations.
- Immune checkpoint inhibitors provide durable responses in a subset of patients.
- Identifying patients who will benefit from immunotherapy is a key challenge.
Conclusions:
- Targeted therapies and immunotherapies have revolutionized advanced melanoma care.
- The pathologist plays a critical role in patient selection for both treatment modalities.