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A 3D Organotypic Melanoma Spheroid Skin Model
Published on: May 18, 2018
The Rapid Emergence of Novel Therapeutics in Advanced Malignant Melanoma
Lijo John1, C Lance Cowey2,3,4
1Baylor-Sammons Cancer Center, Texas Oncology, P.A., Dallas, TX, USA.
Abstract:
For decades, no cancer therapy had been shown to improve average survival in metastatic melanoma. Two critical events have occurred, the discovery of melanoma driver mutation subsets and the discovery of immune checkpoint inhibitors, which have allowed for the development of modern, effective therapies. These findings have facilitated a rapid emergence of novel therapeutics for the disease with multiple FDA approvals in the last several years. The drugs vemurafenib, trametinib, and dabrafenib, which inhibit the commonly mutated BRAF pathway, have been approved based on improvements in survival outcomes. Agents that block immune checkpoints on lymphocytes allowing for immune cell activity against melanoma have also been approved based on improved survival outcomes such as ipilimumab and nivolumab. Pembrolizumab, another immune checkpoint inhibitor, has also been approved based on the response rate and duration of response in a phase 1 trial. Further agents and combinations of approved agents are positioned to possibly further increase this tally of approved drugs. This review will discuss recently approved novel agents and select drugs in development in advanced melanoma.
Insights
Advances in understanding melanoma mutations and immune checkpoint inhibitors have led to new, effective therapies. Several BRAF pathway inhibitors and immune checkpoint blockers have significantly improved survival in metastatic melanoma patients.
Area of Science:
- Oncology
- Immunology
- Dermatology
Background:
- Metastatic melanoma historically lacked effective treatments improving overall survival.
- Recent breakthroughs include identifying melanoma driver mutations and developing immune checkpoint inhibitors.
Purpose of the Study:
- To review novel therapeutic agents recently approved for advanced melanoma.
- To discuss select drugs currently in development for metastatic melanoma treatment.
Main Methods:
- Review of recent FDA approvals for melanoma therapies.
- Analysis of clinical trial data for BRAF pathway inhibitors and immune checkpoint inhibitors.
- Discussion of emerging therapeutic strategies and combination treatments.
Main Results:
- Multiple novel therapeutics have received FDA approval, including BRAF inhibitors (vemurafenib, dabrafenib) and trametinib.
- Immune checkpoint inhibitors (ipilimumab, nivolumab, pembrolizumab) have demonstrated improved survival outcomes.
- Pembrolizumab approval was based on response rate and duration in a Phase 1 trial.
Conclusions:
- Significant progress has been made in treating advanced melanoma due to targeted therapies and immunotherapy.
- Further development of agents and combination therapies holds promise for improving patient survival.
- The landscape of melanoma treatment has been transformed by these novel therapeutic approaches.
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