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Updates on Molecular Targeted Therapies for Intraparenchymal CNS Metastases
Akanksha Sharma1, Lauren Singer2, Priya Kumthekar2
1Department of Translational Neurosciences, Pacific Neuroscience Institute, Saint John Cancer Institute, Santa Monica, CA 90404, USA.
Abstract:
Central nervous system (CNS) metastases can occur in a high percentage of systemic cancer patients and is a major cause of morbidity and mortality in these patients. Almost any histology can find its way to the brain, but lung, breast, and melanoma are the most common pathologies seen in the CNS from metastatic disease. Identification of many key targets in the tumorigenesis pathway has been crucial to the development of a number of drugs that have demonstrated successful penetration of the blood-brain, blood-cerebrospinal fluid, and blood-tumor barriers. Targeted therapy and immunotherapy have dramatically revolutionized the field with treatment options that can provide successful and durable control of even CNS disease. In this review, we discuss major targets with successful treatment options as demonstrated in clinical trials. These include tyrosine kinase inhibitors, monoclonal antibodies, and antibody-drug conjugates. We also provide an update on the state of the field and highlight key upcoming trials. Patient-specific molecular information combined with novel therapeutic approaches and new agents has demonstrated and continues to promise significant progress in the management of patients with CNS metastases.
Insights
Central nervous system (CNS) metastases are common in cancer patients. Targeted therapies and immunotherapies show promise for durable control of CNS disease.
Area of Science:
- Oncology
- Neurology
- Pharmacology
Background:
- Central nervous system (CNS) metastases are a significant cause of morbidity and mortality in systemic cancer patients.
- Lung, breast, and melanoma cancers are the most common origins of CNS metastases.
- Overcoming the blood-brain barrier is critical for effective CNS cancer treatment.
Purpose of the Study:
- To review current targeted therapies and immunotherapies for CNS metastases.
- To discuss major targets with successful clinical trial outcomes.
- To provide an update on the field and highlight future clinical trials.
Main Methods:
- Review of clinical trials and therapeutic approaches for CNS metastases.
- Discussion of drug classes including tyrosine kinase inhibitors, monoclonal antibodies, and antibody-drug conjugates.
- Analysis of molecular targets and their role in CNS tumorigenesis.
Main Results:
- Targeted therapies and immunotherapies have revolutionized CNS metastasis treatment.
- Several drug classes demonstrate successful penetration of CNS barriers.
- Durable control of CNS disease is achievable with modern treatments.
Conclusions:
- Patient-specific molecular information combined with novel therapies offers significant progress.
- Targeted therapy and immunotherapy represent a paradigm shift in managing CNS metastases.
- Ongoing research and clinical trials promise further advancements in CNS cancer care.
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