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Hybrid PET/MRI Imaging of Alzheimer's Disease Based on 18F-AV-1451
Published on: April 18, 2025
Oncology drug repurposing as a blueprint for Alzheimer's therapy
Viswanath Das1,2, Marián Hajdúch1,2
1Institute of Molecular and Translational Medicine, Faculty of Medicine and Dentistry Palacký University and University Hospital Olomouc Olomouc Czech Republic.
Abstract:
Alzheimer's disease (AD) imposes substantial personal, social, and economic burdens, yet current therapies provide only modest slowing of clinical decline. Recent approvals of amyloid-targeting antibodies confirm target engagement but also expose the limitations of single-target strategies in a disease shaped by interacting processes, including amyloid pathology, tau aggregation, neuroinflammation, vascular dysfunction, and metabolic disturbances. These limitations suggest that therapeutic approaches should target multiple pathways rather than isolated lesions. Over the past two decades, cancer therapy has shifted toward rational combinations, multi-target interventions, drug repurposing, and adaptive trial designs. Several of these principles are directly relevant to AD. Recent studies, including work showing that combinations of approved anticancer agents can reverse AD-related network dysfunction across multiple brain cell types, suggest that repurposing oncology drugs for neurodegeneration is biologically plausible. An added advantage is that repurposing builds on existing safety, pharmacokinetic, and clinical experience, which may reduce development time and cost. In this Perspective, we discuss how oncology-informed repurposing strategies, combined with biomarker-based enrichment, system-level pharmacology, and adaptive platform trials, could support more integrated therapeutic development for AD. We also consider practical translational and regulatory issues, including expectations for demonstrating combination benefit, managing drug-drug interactions, and navigating intellectual property pathways. Together, these cross-disciplinary strategies offer a realistic path toward treatments that can produce durable, population-level benefits.
Insights
Repurposing cancer drugs may offer a new strategy for Alzheimer's disease (AD) treatment. Combining therapies targeting multiple disease pathways could lead to more effective, durable benefits for patients.
Area of Science:
- Neuroscience
- Oncology
- Pharmacology
Background:
- Alzheimer's disease (AD) presents significant burdens, with current treatments offering limited efficacy.
- Single-target strategies for AD are insufficient due to the disease's complex, multifactorial nature involving amyloid, tau, neuroinflammation, vascular, and metabolic pathways.
Purpose of the Study:
- To explore oncology-informed drug repurposing strategies for Alzheimer's disease treatment.
- To advocate for integrated therapeutic development using multi-target interventions and adaptive trial designs.
Main Methods:
- Leveraging principles from cancer therapy, including rational combinations and drug repurposing.
- Applying biomarker-based enrichment, system-level pharmacology, and adaptive platform trials to AD drug development.
- Considering translational and regulatory challenges for combination therapies.
Main Results:
- Recent studies suggest repurposing approved anticancer agents can reverse AD-related network dysfunction.
- Oncology drug repurposing builds on existing safety and pharmacokinetic data, potentially reducing development time and cost.
Conclusions:
- Integrated therapeutic development for AD, informed by oncology strategies, offers a realistic path toward more effective treatments.
- Cross-disciplinary approaches combining multi-target interventions, biomarker enrichment, and adaptive trials can yield durable, population-level benefits for Alzheimer's disease.
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