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A 3D Organotypic Melanoma Spheroid Skin Model
Published on: May 18, 2018
What Is the Timing and Role of Targeted Therapy in Metastatic Melanoma?
Matthew J Hadfield1, Ryan J Sullivan2
1From the Brown University/Legorreta Cancer Center, Providence, RI.
Abstract:
Melanoma is the most lethal cutaneous malignancy worldwide. The last 15 years have ushered in several regulatory approvals that have dramatically altered the landscape of treatment options for patients with melanoma. Many patients with melanoma harbor activating mutations in the BRAF proto-oncogene, a key component of the mitogen-activated protein kinase (MAPK) intracellular signaling pathway. Therapies targeting BRAF have led to remarkable improvements in both response rates and survival in patients with metastatic disease. In parallel with these developments in MAPK-targeted therapy has been the clinical development of immune checkpoint inhibitors, which also have improved response rates and survival in patients with metastatic disease including randomized trials compared with MAPK-targeted therapy in patients with advanced, BRAF-mutant melanoma. Immune checkpoint inhibitors have become the preferred first-line standard-of-care treatment for patients with newly diagnosed metastatic disease in patients irrespective of BRAF mutational status. Given these developments, it is now less clear how to optimize the use of MAPK-targeted therapy regarding treatment setting and in sequence with immune checkpoint inhibitor.
Insights
Melanoma treatment has advanced with BRAF-targeted therapies and immune checkpoint inhibitors, improving survival for metastatic disease. Optimizing the sequence of these treatments, especially for BRAF-mutant melanoma, remains a key clinical question.
Area of Science:
- Oncology
- Dermatology
- Immunology
Background:
- Melanoma is a deadly skin cancer with recent therapeutic advancements.
- BRAF mutations are common in melanoma and targeted by specific therapies.
- Immune checkpoint inhibitors (ICIs) have also shown efficacy in metastatic melanoma.
Purpose of the Study:
- To review the impact of BRAF-targeted therapy and ICIs on melanoma treatment.
- To discuss the current standard of care for metastatic melanoma.
- To explore optimal sequencing strategies for BRAF inhibitors and ICIs.
Main Methods:
- Review of recent clinical trials and regulatory approvals in melanoma treatment.
- Analysis of response rates and survival data for different therapeutic modalities.
- Discussion of treatment guidelines and emerging evidence.
Main Results:
- BRAF-targeted therapies significantly improved outcomes in BRAF-mutant metastatic melanoma.
- ICIs have demonstrated improved response rates and survival, becoming first-line treatment.
- Randomized trials show ICIs are effective regardless of BRAF mutation status.
Conclusions:
- ICIs are now the preferred first-line treatment for metastatic melanoma.
- The optimal role and sequencing of MAPK-targeted therapy with ICIs require further investigation.
- Personalized treatment strategies are crucial for managing advanced melanoma.
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