Table 2 Anticancer drug class, mechanism of action, approved indications, and therapeutic rationale for repurposing in Alzheimer’s disease

Vorinostat

HDAC inhibitor

Antiproliferative effect through modulation of histone acetylase activity

Cutaneous manifestations in cutaneous T cell lymphoma

Restoration of synaptic plasticity.

Improved memory long-term potentiation, reduction in Aβ and tau pathology.

[24, 25]

Bosutinib

Tyrosine kinase inhibitor

The primary target is the BCR-ABL kinase. Inhibition of several tyrosine kinases

Ph+ chromosome chronic myeloid leukemia

Increase in blood and brain IL-10 and soluble CX3CL1

[26,27,28,29]

Masitinib

Tyrosine kinase inhibitor

Inhibition of the receptor tyrosine kinase c-Kit. Inhibition of PDGFR, Lck, FAK, and FGFR3

Mast cell tumor (for veterinary use)

Inhibition of c-Kit receptor in MCs. It is capable of blocking Fyn that is involved in tau phosphorylation. Cognitive improvements as a result of Fyn inhibition

[30,31,32,33,34]

Dasatinib

Tyrosine kinase inhibitor

Inhibition of BCR-ABL, SRC family kinases, c-Kit, EPHA2, and PDGFRβ

Ph+ chromosome chronic myeloid leukemia in chronic phase and acute lymphoblastic leukemia in blastic phase

Removal of senescent cells from the plaque environment.

Inhibition of amyloid-dependent microgliosis

[35, 36]

Nilotinib

Tyrosine kinase inhibitor

Antiproliferative effects through inhibition of several kinases (BCR-ABL, c-Kit and PDGF, PI3K-Akt, JACK-STAT)

Ph+ chromosome chronic myeloid leukemia

Abl inhibition facilitates amyloid clearance and reduces inflammation. Upregulation of soluble CX3CL1

[26,27,28]

Pexidartinib

Tyrosine kinase inhibitor

It works by inhibiting the colony-stimulating factor (CSF1)/CSF1 receptor pathway.

Symptomatic tenosynovial giant cell tumor

Reduction in microglial neuroinflammation

[37,38,39,40]

Bexarotene

Retinoid X receptor agonist

Inhibition of cell cycle progression, prevention of multidrug resistance, inhibition of angiogenesis and metastasis

Advanced cutaneous T-cell lymphoma

Alter the CSF levels of ApoE

Inhibition of Aβ42 aggregation

[21, 41,42,43,44]

Tamibarotene

Retinoid X receptor agonist

Specific agonist for retinoic acid receptor alpha/beta with possible binding to retinoid X receptors (RXR)

Relapsed or refractory acute promyelocytic leukemia (only in Japan)

Decreased insoluble Aβ 42 deposition in and increased VAChT and ACh in the brain and reduction of neuroinflammation

[45]

Thalidomide

Immunomodulatory agent

Possible anti-TNF-α effects.

It may act as a VEGF inhibitor.

Multiple myeloma

Reduction of Αβ, inhibition of the expression of BACE1 enzyme. Reduction of proinflammatory TNF-α

[46]

Lenalidomide

Immunomodulatory agent

Tumor cell apoptosis by inhibition of bone marrow stromal cell support, by anti-angiogenic, anti-osteoclastogenic effects, and by immunomodulatory activity

Multiple myeloma; mantle cell lymphoma; follicular lymphoma

Reduction of the expression of TNF-α, IL-6, IL-8

Increase the expression of anti-inflammatory cytokines.

[47, 48]

Daratumumab

Monoclonal antibody

Targeting and induction of apoptosis in cells that highly express CD38

Relapse/refractory

Multiple myeloma

AD pathology is attenuated in CD38-deficient mouse model

[49, 50]