Discovering Potential in Non-Cancer Medications: A Promising Breakthrough for Multiple Myeloma Patients
Abstract
:Simple Summary
Abstract
1. The Significance of Repurposing
2. Pharmacological Repurposing Strategies and Tools
3. Medicines That Could Be Repurposed to Treat MM
3.1. Thalidomide
3.2. Statins
3.3. Celecoxib
3.4. Aspirin
3.5. Clarithromycin
3.6. Rapamycin
3.7. Valproic Acid
3.8. Nelfinavir
3.9. Metformin
3.10. Bisphosphonates
3.11. CuET
3.12. Albendazole
4. Conclusions and Future Prospectives
5. Practice Points
- Although there have been numerous clinical trials conducted to evaluate different approaches for treating cancer, the 5-year survival rate for individuals with MM in the US remains at a modest 55%.
- Myeloma remains a challenging malignancy to treat due to the development of drug resistance, resulting in relapse for all patients.
- There is an ongoing demand for new medications. However, the process of finding a new treatment can often be quite time-consuming. Therefore, repurposing already approved non-cancer medication for MM can aid in the discovery of new effective drugs.
- The potential for repurposing approved drugs is promising, although a thorough analysis of these agents is necessary before they can be considered for clinical trials.
6. Research Agenda
- The potential of various non-anti-cancer drugs as an anti-myeloma treatment was discussed.
- Thalidomide stands out as an exemplary repurposed agent for treating MM.
- There is encouraging evidence that statins, rapamycin, clarithromycin, and leflunomide can inhibit MM.
- Extensive animal studies using the MM animal model, along with phase 1 clinical studies, are necessary to thoroughly investigate these agents as potential MM therapies.
Author Contributions
Funding
Conflicts of Interest
References
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Purpose | Resource | Refs. |
---|---|---|
Human pathways and protein–protein interaction (PPI) | BiGRID, STRING, HAPPI, KEGG, Reactome | [27,28,29,30,31] |
Molecular classification of more than 20,000 main cancers matched normal tissue from 33 types of cancer | Cancer Genome Atlas | [32] |
Protein expression in cancer, matched normal tissues, and human cancer cell lines | The Human Protein Atlas | [33,34,35] |
Drug sensitivity, gene expression, and genotype for human cancer cell lines | Cancer Cell Line Encyclopedia | [36] |
Data of genome-wide transcription expression from cultured human cancer cells with many small compounds | Connectivity Map 02 (CMap) | [37,38] |
Disease-specific gene curation and analysis | OMIM, GEO | [39,40] |
Disease–disease connectivity; connectivity of two genes elaborated within the same disease | The human disease network | [40] |
Disease similarities as seen through the lens of gene regulatory mechanisms; comprehension of disease etiology and pathophysiology | Human Disease Network Database (DNetDB) | [41] |
Drug–drug interaction; comprehensive drug-target information on tens of thousands of drugs and targets | DrugBank | [42] |
Drug–drug interaction | SFINX | [43] |
Database of more than 270 non-cancer drugs for potential repurposing for anti-cancer therapy | Repurposing Drugs in Oncology (ReDO) | [44] |
Database of drugs and adverse drug reactions (ADRs) | Side Effect Resource (SIDER) | [45] |
Withdrawn or discontinued drugs | WITHDRAWN | [46,47] |
An inventory of main and secondary uses for repurposed pharmaceuticals | RepurposeDB | [48] |
Chemical (including drugs)–protein interaction network | STITCH | [47] |
Data on the sensitivity of hundreds of compounds and over a thousand cancer cell lines | Genomics of Drug Sensitivity in Cancer (GDSC) | [49] |
Gene expression pattern-based prediction of drug effectiveness against cancer | DeSigN | [50] |
Drug Name | Old-Indication | New-Indication | Mechanism of Action | Clinical Trials Status | Refs. |
---|---|---|---|---|---|
Thalidomide | Sedative, anti-nausea | MM | Inhibits IKK (also NF-κB); inhibits TNF; inhibits IL-1, IL-6, IL-12, VEGF | Approved in combination with dexamethasone | [51,52] |
Statins | High Cholesterol | MM | HMG-CoA reductase inhibitors, upregulation of PUMA and NOXA | Smouldering MM, phase II | [53,54,55,56] |
Celecoxib | Anti- inflammatory | MM and drug-resistant MM | Inhibits COX-2, inhibits Mcl-1, Bcl-2, survivin, Akt | Not for MM, approved for FAP | [57,58,59] |
Aspirin | Anti- inflammatory | MM | Inhibits COX-1 and COX-2, suppresses cytokines and NF-κB, inhibits EKR and Blimp1, activates ATF4/CHOP | Preclinical | [60,61] |
Artesunate | Malaria | MM and drug-resistant MM | Decreased expression of MYC and Bcl-2, triggers cleavage of caspase-3 | Preclinical | [62,63,64,65] |
Leflunomide | Rheumatism | MM | DHODH inhibitor, cyclin D2 and pRb inhibition | Phase II | [66,67] |
Clarithromycin | Antibiotic | MM and drug-resistant MM | Inhibits IL-6 and MGFs | Phase III | [68,69] |
Rapamycin | Fungal infections | MM | Antagonist of mTOR | Phase I | [70,71,72,73] |
Valproic acid | Seizures, migraine, and epilepsy | MM | Blocks HDAC, inhibits NF-κB and cytokines | Preclinical | [74] |
Nelfinavir | HIV Infection | MM and drug-resistant MM | Inhibits 26S proteasome- disrupts Akt and STAT3, ERK1/2 | Phase I | [75,76,77,78] |
Metformin | Diabetes mellitus type 2 | MM | Activates AMPK (suppresses mTORC1, activates p53), inhibits EMT, regulates cell cycle proteins (ERK1/2, JAK2/STAT), IL-6 suppression | Smoldering Myeloma and Monoclonal gammopathy of undetermined significance phase II, MM phase I | [77,79,80,81] |
Bisphosphonates | Osteoporosis | MM | HMG-CoA pathway suppression, osteoclast apoptosis | Preclinical | [82,83] |
CuET | Alcohol-abuse drug disulfiram (DSF) | Drug-resistant MM | ALDH inhibition | Preclinical | [84] |
Albendazole | Parasitic infections | Drug-resistant MM | Microtubule system interference, p65/NF-κB pathway inhibition | Preclinical | [85] |
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Share and Cite
Al-Odat, O.S.; Nelson, E.; Budak-Alpdogan, T.; Jonnalagadda, S.C.; Desai, D.; Pandey, M.K. Discovering Potential in Non-Cancer Medications: A Promising Breakthrough for Multiple Myeloma Patients. Cancers 2024, 16, 2381. https://doi.org/10.3390/cancers16132381
Al-Odat OS, Nelson E, Budak-Alpdogan T, Jonnalagadda SC, Desai D, Pandey MK. Discovering Potential in Non-Cancer Medications: A Promising Breakthrough for Multiple Myeloma Patients. Cancers. 2024; 16(13):2381. https://doi.org/10.3390/cancers16132381
Chicago/Turabian StyleAl-Odat, Omar S., Emily Nelson, Tulin Budak-Alpdogan, Subash C. Jonnalagadda, Dhimant Desai, and Manoj K. Pandey. 2024. "Discovering Potential in Non-Cancer Medications: A Promising Breakthrough for Multiple Myeloma Patients" Cancers 16, no. 13: 2381. https://doi.org/10.3390/cancers16132381
APA StyleAl-Odat, O. S., Nelson, E., Budak-Alpdogan, T., Jonnalagadda, S. C., Desai, D., & Pandey, M. K. (2024). Discovering Potential in Non-Cancer Medications: A Promising Breakthrough for Multiple Myeloma Patients. Cancers, 16(13), 2381. https://doi.org/10.3390/cancers16132381