Do Cancer Drugs Counteract Neurodegeneration? Repurposing for Alzheimer's Disease.
In spite of in depth investigations in the field of the amyloid cascade hypothesis, so far, no disease modifying therapy has been developed for Alzheimer's disease (AD). The pathophysiology provides some evidence of the inverse correlation between cancer and AD. Both AD and cancer are characterized by abnormal cellular behaviors; trigger factors along with a meta synchronously action is expected to drive cancer or neurodegeneration, supporting, respectively, progressive neuronal loss or uncontrolled cell proliferation in cancer cells. So far, cancer and AD are seemingly two opposite ends of the same biological spectrum. Basic science increasingly indicates shared molecular mechanisms between cancer and AD and gives weight to key relevant biological theories; according to them, the inverse tuning of clustered gene expression, the sharing of mutual independent pathway or the deregulated unfolded proteins system (UPR) may count for this inverse association. Additionally, the common biological background gave credibility to the recent discovery of a repurposing role for cancer drugs in AD. It refers to the development of new uses for existing pharmaceuticals having the same role as the original mechanism or to the discovery of a new drug action with disease modifying effects. The present review summarizes the most important biological theories that link neurodegeneration and cancer and provides an up-to-date revision of the repurposing cancer agents for AD. The review also addresses the gap of knowledge, since drug cancer repositioning holds an important promise but further investigations are warranted to ascertain the clinical relevance of such attractive clinical candidate compounds for AD.
Section of Geriatrics, Department of Internal Medicine and Medical Specialties (DIMI), University of Genoa, Genoa, Italy.
Fiammetta
F
Monacelli
Section of Haematology, Department of Internal Medicine and Medical Specialties, (DIMI), University of Genoa, Genoa, Italy.
Michele
M
Cea
Section of Geriatrics, Department of Internal Medicine and Medical Specialties (DIMI), University of Genoa, Genoa, Italy.
Roberta
R
Borghi
Section of Geriatrics, Department of Internal Medicine and Medical Specialties (DIMI), University of Genoa, Genoa, Italy.
Patrizio
P
Odetti
Section of Geriatrics, Department of Internal Medicine and Medical Specialties (DIMI), University of Genoa, Genoa, Italy.
Alessio
A
Nencioni
D000970:Antineoplastic Agents / Q000627:therapeutic use*; D058492:Drug Repositioning; D006801:Humans; D019636:Neurodegenerative Diseases / Q000188:drug therapy*
D000970:Antineoplastic Agents
Alzheimer’s disease; cancer repurposing drugs