The key characteristics of representative repurposed drugs.
| Drug class | Representative agents | Original indication | Proposed anticancer mechanisms | Key synergistic partners | Clinical status/evidence level | Refs. |
|---|---|---|---|---|---|---|
| Biguanides | Metformin | Type 2 diabetes | AMPK/mTOR inhibition; TME modulation; PD-L1 downregulation | Chemotherapy (temozolomide, cisplatin); ICIs | Phase II/III; epidemiological support | [37–44, 122–124] |
| Statins | Atorvastatin, Simvastatin | Hypercholesterolemia | Mevalonate pathway inhibition; disrupts Ras/Rho prenylation | Chemotherapy; targeted therapy | Phase II ongoing; preclinical | [8, 45, 115] |
| Antimalarials | Artemisinin, CQ, HCQ | Malaria | Ferroptosis induction; autophagy inhibition (CQ/HCQ) | Chemotherapy (doxorubicin); radiotherapy | Phase II (mixed); repurposing challenges | [16, 55, 69, 70] |
| β-Blockers | Propranolol | Hypertension, arrhythmia | β-Adrenergic blockade; anti-angiogenic; immune modulation | Chemotherapy (5-fluorouracil) | Preclinical; retrospective observations | [50, 52, 53] |
| Antihistamines | Cetirizine, Loratadine | Allergies | HRH1 receptor blockade; restores CD8+ T cell activity | ICIs | Observational; potential ICI adjuvant | [54] |
| NSAIDs | Aspirin, Celecoxib | Inflammation, pain | COX-2/PGE2 inhibition; converts “cold” tumors to “hot” | Immunotherapy (ICIs) | Preclinical; combination studies ongoing | [57, 125–127] |
| HDAC Inhibitors | Valproic acid | Epilepsy | HDAC inhibition; chromatin relaxation; gene reactivation | Chemotherapy (gemcitabine) | Phase II (e.g., VESPA trial) | [62–64, 112, 115] |
| Antipsychotics | Pimozide, Fluphenazine, Sertraline | Psychiatric disorders | MDR inhibition (P-glycoprotein [P-gp]); apoptosis induction; SHMT inhibition (sertraline) | Chemotherapy (paclitaxel); mitochondrial inhibitors | Preclinical; early clinical exploration | [72–75] |
| Cardiovascular Drugs | Digoxin, Verapamil | Heart failure, arrhythmia | Na+/K+-ATPase inhibition; calcium channel blockade | Chemotherapy | Preclinical | [76–78] |
AMPK: AMP-activated protein kinase; COX-2: cyclooxygenase-2; CQ: chloroquine; HCQ: hydroxychloroquine; HDAC: histone deacetylase; ICIs: immune checkpoint inhibitors; mTOR: mechanistic target of rapamycin; PD-L1: programmed death ligand 1; PGE2: prostaglandin E2; TME: tumor microenvironment.
JY: Conceptualization, Writing—original draft, Writing—review & editing. XW: Conceptualization, Writing—original draft, Writing—review & editing. XZ: Investigation, Writing—review & editing. SZ: Investigation, Writing—review & editing. DX: Validation, Writing—review & editing. ZT: Validation, Writing—review & editing. ZY: Formal analysis, Writing—review & editing. CZ: Supervision, Project administration, Writing—review & editing, Funding acquisition. All authors read and approved the submitted version.
The authors declare that they have no conflicts of interest.
Not applicable.
Not applicable.
Not applicable.
All data supporting the findings of this review are included within the article and its references.
This review article was conducted as part of a thesis project funded by Natural Science Foundation of the Higher Education Institutions of Anhui Province (2025AHGXZK30987), National university innovation and entrepreneurship training program (2025103668067, 202610368018, 202610368077), Anhui Province university innovation and entrepreneurship training program (S202510368021, S202510368118). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
© The Author(s) 2026.
Open Exploration maintains a neutral stance on jurisdictional claims in published institutional affiliations and maps. All opinions expressed in this article are the personal views of the author(s) and do not represent the stance of the editorial team or the publisher.