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Novel strategies to overcome the blood–brain barrier in triple-negative breast cancer brain metastases
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DOI：10.1016/S1470-2045(26)00146-4.png)
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Abstract
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Triple-negative breast cancer—the most aggressive breast cancer subtype—has a high propensity for brain metastases, with limited treatments and poor prognosis. The blood–brain barrier, long viewed as an impermeable therapeutic sanctuary, is the core barrier to effective care. This Review advocates a key paradigm shift for clinical and translational research: from merely circumventing the blood–brain barrier to actively targeting and exploiting its biology. We delineate triple-negative breast cancer-specific mechanisms of blood–brain barrier breach and evaluate emerging therapies via a clinically actionable three-pillar framework: physical and focal blood–brain barrier disruption, biological blood–brain barrier exploitation, and microenvironmental modulation. We also summarise advances in preclinical models for blood–brain barrier-targeted drug development. Synthesising the latest preclinical and clinical evidence, this Review provides a translational roadmap for unmet clinical needs, emphasising that integrated, blood–brain barrier-centric strategies are crucial to improving patient outcomes.
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