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Implantation and Monitoring by PET/CT of an Orthotopic Model of Human Pleural Mesothelioma in Athymic Mice
Published on: December 21, 2019
Targeted Approaches to Treatment of Pleural Mesothelioma: A Review
1Department of Medicine, Massachusetts General Hospital Cancer Center, Massachusetts General Hospital, Boston, MA.
Abstract:
Pleural mesothelioma is an aggressive disease that is enriched for inactivating alterations in tumor suppressor genes. Systemic therapeutic strategies for pleural mesothelioma generally involve chemotherapies and immunotherapies that are chosen without consideration of the tumor's molecular profile. As this generalized approach to treatment rarely yields durable responses, alternative therapeutic regimens are urgently indicated. Preclinical studies have identified synthetic lethal protein and metabolic interactions, recurrently overexpressed proteins, and frequent pathway perturbations that may be therapeutically exploited in mesothelioma. This review discusses the mechanism of action of emerging investigational therapies and summarizes findings from phase I-II clinical trials exploring selective, biomarker-driven therapeutic strategies for mesothelioma, with a focus on five common targets. Finally, using lessons learned from these clinical trials, imperatives for successful implementation of targeted therapy in mesothelioma are discussed.
Insights
Targeted therapies offer new hope for pleural mesothelioma patients by focusing on specific molecular targets, moving beyond traditional chemotherapy. This approach aims to improve durable responses in this aggressive cancer.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Pleural mesothelioma is an aggressive cancer characterized by tumor suppressor gene alterations.
- Current systemic treatments lack molecular profiling, leading to limited durable responses.
- There is an urgent need for alternative therapeutic strategies.
Purpose of the Study:
- To review emerging investigational therapies for pleural mesothelioma.
- To summarize findings from Phase I-II clinical trials of targeted therapies.
- To discuss imperatives for implementing biomarker-driven treatment strategies.
Main Methods:
- Review of preclinical studies identifying therapeutic targets in mesothelioma.
- Analysis of Phase I-II clinical trial data for emerging therapies.
- Focus on five common molecular targets in pleural mesothelioma.
Main Results:
- Preclinical data suggest exploitability of synthetic lethal interactions, overexpressed proteins, and pathway perturbations.
- Emerging therapies show promise in early-phase clinical trials.
- Biomarker-driven strategies are being explored for mesothelioma treatment.
Conclusions:
- Targeted therapies represent a promising alternative to conventional treatments for pleural mesothelioma.
- Biomarker-driven approaches are crucial for improving patient outcomes.
- Lessons learned from clinical trials are essential for successful targeted therapy implementation.
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