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Published on: May 18, 2018
Targeted therapy and immunotherapy: Emerging biomarkers in metastatic melanoma
Patricia M LoRusso1, Kurt Schalper2, Jeffrey Sosman3
1Department of Medical Oncology, Yale University, New Haven, CT, USA.
Abstract:
Targeted therapy directed against oncogenic BRAF mutations and immune checkpoint inhibitors have transformed melanoma therapy over the past decade and prominently improved patient outcomes. However, not all patients will respond to targeted therapy or immunotherapy and many relapse after initially responding to treatment. This unmet need presents two major challenges. First, can we elucidate novel oncogenic drivers to provide new therapeutic targets? Second, can we identify patients who are most likely to respond to current therapeutic strategies in order to both more accurately select populations and avoid undue drug exposure in patients unlikely to respond? In an effort to evaluate the current state of the field with respect to these questions, we provide an overview of some common oncogenic mutations in patients with metastatic melanoma and ongoing efforts to therapeutically target these populations, as well as a discussion of biomarkers for response to immune checkpoint inhibitors-including tumor programmed death ligand 1 expression and the future use of neoantigens as a means of truly personalized therapy. This information is becoming important in treatment decision making and provides the framework for a treatment algorithm based on the current landscape in metastatic melanoma.
Insights
Targeted therapy and immunotherapy have advanced melanoma treatment, but patient response varies. Research aims to find new targets and biomarkers for better patient selection and personalized melanoma therapy.
Area of Science:
- Oncology
- Immunology
- Genetics
Background:
- Targeted therapy for BRAF mutations and immune checkpoint inhibitors have significantly improved outcomes in metastatic melanoma.
- However, a substantial number of patients do not respond or eventually relapse, highlighting an unmet clinical need.
Purpose of the Study:
- To review current oncogenic drivers in metastatic melanoma and therapeutic strategies.
- To discuss biomarkers for immune checkpoint inhibitor response and explore future personalized therapy approaches.
Main Methods:
- Literature review of common oncogenic mutations in metastatic melanoma.
- Analysis of ongoing therapeutic targeting efforts.
- Discussion of biomarkers such as tumor programmed death ligand 1 (PD-L1) expression and neoantigens.
Main Results:
- BRAF mutations are a common target, with ongoing development of novel therapies.
- Immune checkpoint inhibitors show promise, with PD-L1 expression and neoantigens emerging as predictive biomarkers.
- Personalized therapy strategies are crucial for optimizing treatment selection.
Conclusions:
- Identifying novel oncogenic drivers and predictive biomarkers is essential for improving metastatic melanoma treatment.
- A personalized treatment algorithm based on molecular profiling and biomarker status can guide clinical decision-making.
- Further research into neoantigens holds potential for truly individualized melanoma therapy.
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