Repurposing Non-oncology Small-molecule Drugs to Improve Cancer Therapy: Current Situation and Future Directions

Overview

Journal Acta Pharm Sin B

Publisher Elsevier

Specialty Pharmacology

Date 2022 Mar 8

PMID 35256933

Authors

Leilei Fu

Wenke Jin

Jiahui Zhang

Lingjuan Zhu

Jia Lu

Yongqi Zhen

Lan Zhang

Liang Ouyang

Bo Liu

Haiyang Yu

Affiliations

Soon will be listed here.

Abstract

Drug repurposing or repositioning has been well-known to refer to the therapeutic applications of a drug for another indication other than it was originally approved for. Repurposing non-oncology small-molecule drugs has been increasingly becoming an attractive approach to improve cancer therapy, with potentially lower overall costs and shorter timelines. Several non-oncology drugs approved by FDA have been recently reported to treat different types of human cancers, with the aid of some new emerging technologies, such as omics sequencing and artificial intelligence to overcome the bottleneck of drug repurposing. Therefore, in this review, we focus on summarizing the therapeutic potential of non-oncology drugs, including cardiovascular drugs, microbiological drugs, small-molecule antibiotics, anti-viral drugs, anti-inflammatory drugs, anti-neurodegenerative drugs, antipsychotic drugs, antidepressants, and other drugs in human cancers. We also discuss their novel potential targets and relevant signaling pathways of these old non-oncology drugs in cancer therapies. Taken together, these inspiring findings will shed new light on repurposing more non-oncology small-molecule drugs with their intricate molecular mechanisms for future cancer drug discovery.

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References

Fiorillo M, Lamb R, Tanowitz H, Cappello A, Martinez-Outschoorn U, Sotgia F . Bedaquiline, an FDA-approved antibiotic, inhibits mitochondrial function and potently blocks the proliferative expansion of stem-like cancer cells (CSCs). Aging (Albany NY). 2016; 8(8):1593-607. PMC: 5032685. DOI: 10.18632/aging.100983. View

Ahmed M, Jinks N, Babaei-Jadidi R, Kashfi H, Castellanos-Uribe M, May S . Repurposing Antibacterial AM404 as a Potential Anticancer Drug for Targeting Colorectal Cancer Stem-Like Cells. Cancers (Basel). 2020; 12(1). PMC: 7017077. DOI: 10.3390/cancers12010106. View

Efferth T . From ancient herb to modern drug: Artemisia annua and artemisinin for cancer therapy. Semin Cancer Biol. 2017; 46:65-83. DOI: 10.1016/j.semcancer.2017.02.009. View

Marima R, Hull R, Dlamini Z, Penny C . Efavirenz and Lopinavir/Ritonavir Alter Cell Cycle Regulation in Lung Cancer. Front Oncol. 2020; 10:1693. PMC: 7484481. DOI: 10.3389/fonc.2020.01693. View

Zeng L, Wang Y, Kazemi R, Xu S, Xu Z, Sanchez T . Repositioning HIV-1 integrase inhibitors for cancer therapeutics: 1,6-naphthyridine-7-carboxamide as a promising scaffold with drug-like properties. J Med Chem. 2012; 55(22):9492-509. DOI: 10.1021/jm300667v. View

Nowak-Sliwinska P, Scapozza L, Ruiz i Altaba A . Drug repurposing in oncology: Compounds, pathways, phenotypes and computational approaches for colorectal cancer. Biochim Biophys Acta Rev Cancer. 2019; 1871(2):434-454. PMC: 6528778. DOI: 10.1016/j.bbcan.2019.04.005. View

Cho Y, Kim E, Nyiramana M, Shin E, Jin H, Ryu J . Paroxetine Induces Apoptosis of Human Breast Cancer MCF-7 Cells through Ca-and p38 MAP Kinase-Dependent ROS Generation. Cancers (Basel). 2019; 11(1). PMC: 6356564. DOI: 10.3390/cancers11010064. View

Cilibrasi C, Butta V, Riva G, Bentivegna A . Pioglitazone Effect on Glioma Stem Cell Lines: Really a Promising Drug Therapy for Glioblastoma?. PPAR Res. 2016; 2016:7175067. PMC: 4897721. DOI: 10.1155/2016/7175067. View

Dugger B, Dickson D . Pathology of Neurodegenerative Diseases. Cold Spring Harb Perspect Biol. 2017; 9(7). PMC: 5495060. DOI: 10.1101/cshperspect.a028035. View

10.

Agnihotri S, Mansouri S, Burrell K, Li M, Mamatjan Y, Liu J . Ketoconazole and Posaconazole Selectively Target HK2-expressing Glioblastoma Cells. Clin Cancer Res. 2018; 25(2):844-855. PMC: 8103287. DOI: 10.1158/1078-0432.CCR-18-1854. View

11.

Brasky T, Felix A, Cohn D, McMeekin D, Mutch D, Creasman W . Nonsteroidal Anti-inflammatory Drugs and Endometrial Carcinoma Mortality and Recurrence. J Natl Cancer Inst. 2017; 109(3):1-10. PMC: 5161320. DOI: 10.1093/jnci/djw251. View

12.

Abaza Y, Kantarjian H, Garcia-Manero G, Estey E, Borthakur G, Jabbour E . Long-term outcome of acute promyelocytic leukemia treated with all--retinoic acid, arsenic trioxide, and gemtuzumab. Blood. 2016; 129(10):1275-1283. PMC: 5413297. DOI: 10.1182/blood-2016-09-736686. View

13.

Hicks J, Sangkuhl K, Swen J, Ellingrod V, Muller D, Shimoda K . Clinical pharmacogenetics implementation consortium guideline (CPIC) for CYP2D6 and CYP2C19 genotypes and dosing of tricyclic antidepressants: 2016 update. Clin Pharmacol Ther. 2016; 102(1):37-44. PMC: 5478479. DOI: 10.1002/cpt.597. View

14.

Qin G, Zhao C, Zhang L, Liu H, Quan Y, Chai L . Dihydroartemisinin induces apoptosis preferentially via a Bim-mediated intrinsic pathway in hepatocarcinoma cells. Apoptosis. 2015; 20(8):1072-86. DOI: 10.1007/s10495-015-1132-2. View

15.

Wiklund E, Catts V, Catts S, Ng T, Whitaker N, Brown A . Cytotoxic effects of antipsychotic drugs implicate cholesterol homeostasis as a novel chemotherapeutic target. Int J Cancer. 2009; 126(1):28-40. DOI: 10.1002/ijc.24813. View

16.

Overman J, Fontaine F, Wylie-Sears J, Moustaqil M, Huang L, Meurer M . R-propranolol is a small molecule inhibitor of the SOX18 transcription factor in a rare vascular syndrome and hemangioma. Elife. 2019; 8. PMC: 6667216. DOI: 10.7554/eLife.43026. View

17.

Ellegaard A, Dehlendorff C, Vind A, Anand A, Cederkvist L, Petersen N . Repurposing Cationic Amphiphilic Antihistamines for Cancer Treatment. EBioMedicine. 2016; 9:130-139. PMC: 4972561. DOI: 10.1016/j.ebiom.2016.06.013. View

18.

Sanz M, Fenaux P, Tallman M, Estey E, Lowenberg B, Naoe T . Management of acute promyelocytic leukemia: updated recommendations from an expert panel of the European LeukemiaNet. Blood. 2019; 133(15):1630-1643. PMC: 6509567. DOI: 10.1182/blood-2019-01-894980. View

19.

Shchors K, Massaras A, Hanahan D . Dual Targeting of the Autophagic Regulatory Circuitry in Gliomas with Repurposed Drugs Elicits Cell-Lethal Autophagy and Therapeutic Benefit. Cancer Cell. 2015; 28(4):456-471. DOI: 10.1016/j.ccell.2015.08.012. View

20.

Varisli L, Cen O, Vlahopoulos S . Dissecting pharmacological effects of chloroquine in cancer treatment: interference with inflammatory signaling pathways. Immunology. 2019; 159(3):257-278. PMC: 7011648. DOI: 10.1111/imm.13160. View