Repurposing Cancer Drugs for Alzheimer’s: Insights from Rutgers Expert Dr. Marc Tambini

At the Rutgers Brain Health Institute (BHI), we actively collaborate with leading researchers to explore groundbreaking developments in Alzheimer’s disease (AD) treatments. Recently, Dr. Marc D. Tambini, MD, PhD, Assistant Professor at Rutgers Health New Jersey Medical School in the Department of Pharmacology, Physiology & Neuroscience, provided insights into a pivotal new study published in the renowned journal Cell. His commentary sheds light on how researchers are innovatively repurposing existing cancer medications to address Alzheimer’s complex neural networks. Here’s a summary of his expert perspectives.

Introduction: Repurposing Cancer Drugs—A New Path Forward in Alzheimer’s Disease?

Despite decades of rigorous preclinical and clinical research, Alzheimer’s disease drug development has seen a staggering 98% failure rate, with current treatments limited to symptom management. A groundbreaking study published in Cell by Li et al. offers an innovative approach—repurposing two FDA-approved cancer drugs, letrozole and irinotecan, to target Alzheimer’s disease’s complex pathology [1].

Dr. Tambini finds the concept of repurposing cancer drugs both compelling and somewhat surprising, given the historical focus on amyloid-targeted therapies. The study’s innovative use of transcriptomics (gene expression analysis) provides a fresh, cell-type-specific strategy that could shift the paradigm of AD therapeutics.

Summary of Key Findings: Targeting Brain Cell Networks to Improve Memory

The researchers adopted a sophisticated approach, utilizing transcriptomic analyses to categorize Alzheimer’s disease into distinct neuronal and glial cell clusters, each associated with specific dysfunctional pathways. Letrozole was shown to restore critical neuronal networks involved in synaptic signaling, dendritic growth, and metabolic activity. Meanwhile, irinotecan effectively targeted glial cells—specifically astrocytes and microglia—to mitigate neuroinflammation and oxidative stress.

These promising results were demonstrated clearly in AD mouse models. Combined therapy with letrozole and irinotecan effectively reversed key transcriptomic signatures, reduced pathological tau protein aggregates, and notably improved memory performance [1]. From Dr. Tambini’s perspective, the methodological rigor and comprehensive analysis offer convincing evidence that targeting distinct cellular pathways simultaneously holds significant therapeutic potential for Alzheimer’s.

Significance to Neuroscience and Brain Health: A Paradigm Shift in Alzheimer’s Research?

Historically, AD therapies have primarily targeted amyloid-beta plaques. Dr. Tambini highlights how the shift toward addressing specific brain cell network dysfunctions is both novel and significant. This approach aligns with recent genetic insights showing that non-neuronal cells substantially contribute to Alzheimer’s disease etiology.

Moreover, the use of large-scale multimodal patient data underscores the growing potential of AI-driven precision medicine in neuroscience research. Dr. Tambini anticipates that this cell-type-specific, transcriptomics-driven strategy may inspire future neurodegenerative disease research, broadening therapeutic horizons beyond traditional paradigms.

Clinical and Public Relevance: Repurposing Cancer Drugs for Alzheimer’s Treatment

A critical advantage of repurposing FDA-approved cancer drugs is their established clinical profiles. Dr. Tambini notes that, given their existing approval, letrozole and irinotecan could substantially accelerate clinical translation and adoption. Additionally, analysis of electronic health records involving 1.4 million patients revealed decreased Alzheimer’s risk among those previously treated with these cancer medications [1], suggesting real-world applicability.

From a clinical trial perspective, Dr. Tambini emphasizes this could shorten timelines and streamline regulatory processes. For patients and the public, such advancements may invigorate hope and reshape perceptions about achievable progress in Alzheimer’s treatments.

Future Directions and Conclusion: Translating Laboratory Discoveries into Human Benefit

Dr. Tambini acknowledges critical challenges ahead, such as validating findings beyond mouse models—which, due to extensive genetic modifications, may not fully replicate human Alzheimer’s pathology. There’s also the potential risk of unintended side effects, given that not all AD-related gene changes may be detrimental—some may indeed be compensatory.

He emphasizes that moving forward requires meticulous human safety studies, precise trial designs, and deeper analyses of drug impact on human neuronal and glial networks. At Rutgers’ Herbert and Jacqueline Krieger Klein Alzheimer’s Research Center within BHI, Dr. Tambini’s lab further contributes to this vision by exploring cellular trafficking and processing of the Alzheimer’s-related Amyloid Precursor Protein (APP), leveraging discoveries like novel Valosin-containing protein (VCP) inhibitors from ongoing cancer trials [2].

Ultimately, this innovative study marks a transformative step toward a nuanced, transcriptomic-driven understanding of Alzheimer’s, underscoring the immense potential of repurposing established medications to accelerate therapeutic breakthroughs.

Sources:

1. Li et al. (2025). “A Transcriptomic Cell-Type Directed Strategy for Alzheimer’s Disease Treatment.” Cell.
2. Herbert and Jacqueline Krieger Klein Alzheimer’s Research Center, Rutgers Brain Health Institute.