Anticancer drugs repurposed for Alzheimer’s disease: a systematic review

Abstract

Background The relationship between cancer and dementia is triggering growing research interest. Several preclinical studies have provided the biological rationale for the repurposing of specific anticancer agents in Alzheimer’s disease (AD), and a growing number of research protocols are testing their efficacy and safety/tolerability in patients with AD. Methods The aim of the present systematic review was to provide an overview on the repurposing of approved anticancer drugs in clinical trials for AD by considering both ongoing and completed research protocols in all phases. In parallel, a systematic literature review was conducted on PubMed, ISI Web, and the Cochrane Library to identify published clinical studies on repurposed anticancer agents in AD. Results Based on a structured search on the ClinicalTrials.gov and the EudraCT databases, we identified 13 clinical trials testing 11 different approved anticancer agents (five tyrosine kinase inhibitors, two retinoid X receptor agonists, two immunomodulatory agents, one histone deacetylase inhibitor, and one monoclonal antibody) in the AD continuum. The systematic literature search led to the identification of five published studies (one phase I, three phase II, and one phase IIb/III) reporting the effects of antitumoral treatments in patients with mild cognitive impairment or AD dementia. The clinical findings and the methodological characteristics of these studies are described and discussed. Conclusion Anticancer agents are triggering growing interest in the context of repurposed therapies in AD. Several clinical trials are underway, and data are expected to be available in the near future. To date, data emerging from published clinical studies are controversial. The promising results emerging from preclinical studies and identified research protocols should be confirmed and extended by larger, adequately designed, and high-quality clinical trials.

RETRACTED ARTICLE: Polyphenols from Conyza dioscoridis (L.) ameliorate Alzheimer’s disease- like alterations through multi-targeting activities in two animal models

“…They also target β -amyloid. The promising results of preclinical studies have triggered several clinical trials [ 2 , 3 ]. Moreover, Type 2 diabetes mellitus (T2D) has been identified as a high-risk factor for AD [ 4 ].…”

Therapeutic Monitoring of Orally Administered, Small-Molecule Anticancer Medications with Tumor-Specific Cellular Protein Targets in Peripheral Fluid Spaces—A Review

“…It is increasingly acknowledged that certain OACDs may be effective against neurodegenerative and autoimmune diseases [ 9 , 108 ]. Nilotinib, a BCR-ABL tyrosine kinase inhibitor, has been investigated in multiple cases as a medication against mental disorders, such as Parkinson’s disease and Alzheimer’s disease [ 109 , 110 ]. The rationale of these indications is that nilotinib leads to the degradation of misfolded α-synuclein by autophagy [ 111 ].…”

Mapping new pharmacological interventions for cognitive function in Alzheimer’s disease: a systematic review of randomized clinical trials

“…For example, some anticancer drugs such as tyrosine kinase inhibitors and retinoid X receptor agonists can modulate cellular signaling pathways and reduce inflammation, which may be beneficial in the context of AD. Additionally, it has been shown that some anticancer drugs, such as histone deacetylase inhibitors, can improve cognitive function and synaptic plasticity in animal models of AD ( Ancidoni et al, 2021 ). Masitinib is an anti-tumor drug that has been investigated for potential use in the treatment of AD.…”