article · SLAS DISCOVERY
Breast cancer brain metastases present serious clinical challenges and typically carry a poor prognosis. Conventional treatments such as surgery, radiation therapies, and chemotherapy struggle to achieve long-term control because of the protective blood-brain barrier, aggressive metastatic biology, and tumour heterogeneity. Recent developments focus on modern strategies to enhance existing treatments. Nanotechnology-based drug delivery systems, including polymeric nanoparticles and liposomes, offer methods to overcome pharmacokinetic obstacles and improve drug accumulation within the central nervous system. Additionally, combining conventional approaches with immunotherapies, such as immune checkpoint inhibitors and adoptive cell therapies, seeks to strengthen immune responses within the brain microenvironment. Novel radiosensitisers are also under development to counteract radiation resistance. Evidence from preclinical models and clinical trials indicates that combining these modern tools could enhance therapeutic effectiveness, though managing treatment toxicity and creating personalised protocols remain critical hurdles.
Metastatic breast cancer in the brain is difficult to treat and associated with low survival rates. Understanding how modern drug delivery platforms and combination therapies can cross the blood-brain barrier is crucial for designing more effective medical interventions. This knowledge helps direct future clinical strategies toward safer, targeted treatments that can improve patient life expectancy and quality of life.
The approaches highlighted apply to oncology therapeutics and advanced formulation design, specifically for pharmaceutical developers and clinical researchers addressing central nervous system metastases. The described technologies span from preclinical experimental models to active clinical trials, indicating early-stage to translational development. Practical deployment relies on overcoming clinical barriers, specifically controlling therapy-related toxicities and formulating personalised treatment protocols.
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Brain metastasis originating from breast cancer is an uncommon but clinically significant complication that poses substantial therapeutic challenges and is associated with poor patient prognosis. Traditional treatment modalities-including surgical resection, whole-brain radiation therapy, stereotactic radiosurgery, and systemic chemotherapy-often fail to achieve satisfactory long-term control due to the protective nature of the blood-brain barrier (BBB), tumor heterogeneity, and the aggressive biology of metastatic lesions. This comprehensive review delves into recent advances in modern therapeutic approaches that aim to enhance the efficacy of conventional treatments for rare brain metastases from breast cancer (BC). We systematically evaluate emerging strategies such as advanced drug delivery technologies, including nanoparticles (NPs), polymeric NPs, and liposomal formulations, which are designed to overcome pharmacokinetic limitations and improve the penetration and retention of chemotherapeutic agents within the central nervous system (CNS). The review also explores the integration of immunotherapies, particularly immune checkpoint inhibitors and adoptive cell therapies-with traditional modalities to potentiate antitumor immune responses in the brain microenvironment. Moreover, we discuss the development and application of novel radiosensitizers and combination regimens aimed at overcoming the inherent and acquired radioresistance of metastatic tumors. The synthesis of current preclinical models and clinical trial data provides critical insights into the potential of these combined approaches to enhance patient survival and quality of life. Finally, we identify key challenges, including the need for personalized treatment protocols and the management of therapy-related toxicities, and propose future directions for research.
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DOI: 10.1016/j.slasd.2026.100331
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