Theranostic Advancements in Brain Cancer: Promising Approaches for Emerging Therapy

Abstract

Brain cancer, particularly malignant gliomas, poses a formidable clinical challenge due to its high mortality, intratumoral heterogeneity, and resistance to conventional therapies, accounting for substantial global cancer fatalities. Despite decades of research, therapeutic progress remains modest, largely hindered by the blood–brain barrier (BBB) and blood–tumor barrier (BTB), which impede drug delivery and contribute to dismal prognoses. This review addresses the critical gap in integrating diagnostic and therapeutic strategies within a unified theranostic framework for brain cancer management. It systematically examines BBB structural/functional complexities and drug delivery implications, alongside advanced magnetic-resonance imaging (MRI)/positron-emission tomography (PET) for tumor characterization, treatment planning, and response assessment. Emphasis is placed on BBB-crossing strategies, including receptor-mediated transcytosis (RMT), adsorptive-mediated transcytosis (AMT), focused ultrasound (FUS), convection-enhanced delivery (CED), and intra-arterial administration, highlighting mechanistic principles and translational potential. Nanoparticles (NPs)-based systems (polymeric, lipidic, and metallic) are discussed for enhancing bioavailability, overcoming efflux resistance, and enabling multimodal therapies like photodynamic therapy (PDT) and immunotherapy. This review highlights the translational potential of nanotechnology, immuno-oncology, and computational methods in closed-loop theranostic models for real-time monitoring, adaptive therapy, and improved brain cancer survival and quality of life, offering insights to advance clinical outcomes.