Bridging the gap: unlocking the potential of emerging drug therapies for brain metastasis

Nov 8, 2024Brain : a journal of neurology

New drug treatments may help improve care for brain tumors that spread from other cancers

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Abstract

Recent advances in understanding the blood-brain barrier (BBB) have led to strategies that may enhance drug delivery to brain metastases.

The blood-brain barrier and brain-tumour barrier present significant challenges for treating brain metastasis due to their restrictive nature.
Innovative strategies have been developed to improve permeability of the BBB and BTB, potentially allowing more effective drug delivery.
Novel agents, including targeted therapies and immunotherapies, have shown promising intracranial activity against brain metastasis in preclinical and clinical studies.
The review emphasizes the importance of understanding the biological properties of the BBB/BTB for advancing therapeutic approaches.
Considerations for accelerating the clinical translation of new drugs for brain metastasis are discussed.

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Brain metastasis remains an unmet clinical need in advanced cancers with an increasing incidence and poor prognosis. The limited response to various treatments is mainly derived from the presence of the substantive barrier, blood-brain barrier (BBB) and brain-tumour barrier (BTB), which hinders the access of potentially effective therapeutics to the metastatic tumour of the brain. Recently, the understanding of the structural and molecular features of the BBB/BTB has led to the development of efficient strategies to enhance BBB/BTB permeability and deliver drugs across the BBB/BTB to elicit the anti-tumour response against brain metastasis. Meanwhile, novel agents capable of penetrating the BBB have rapidly developed and been evaluated in preclinical studies and clinical trials, with both targeted therapies and immunotherapies demonstrating impressive intracranial activity against brain metastasis. In this review, we summarize the recent advances in the biological properties of the BBB/BTB and the emerging strategies for BBB/BTB permeabilization and drug delivery across the BBB/BTB. We also discuss the emerging targeted therapies and immunotherapies against brain metastasis tested in clinical trials. Additionally, we provide our viewpoints on accelerating clinical translation of novel drugs into clinic for patients of brain metastasis. Although still challenging, we expect this review to benefit the future development of novel therapeutics, specifically from a clinical perspective.

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Bridging the gap: unlocking the potential of emerging drug therapies for brain metastasis

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