Antibody drug conjugates in metastatic brain tumors: current landscape, therapeutic potential and challenges

The management of brain metastases (BrM) remains a major clinical challenge due to limited drug delivery across the blood-brain barrier (BBB) and the need for simultaneous CNS and systemic disease management, often with competing therapeutic strategies. Antibody-drug conjugates (ADCs) are a promising class of drugs that offers precision therapy by combining the specificity of monoclonal antibodies with potent chemotherapeutics for targeted tumor delivery. This review explores the current landscape of ADCs in BrMs, challenges in BBB penetration, and CNS-specific toxicities, including interactions with radiotherapy and the risk of radiation necrosis.