Critical dysregulated signaling pathways in drug resistance: highlighting the repositioning of mebendazole for cancer therapy
BackgroundCancer drug resistance significantly reduces the effectiveness of current anticancer treatments. Multiple dysregulated signaling pathways drive cancer initiation, progression, and related drug resistance. This highlights the need for developing new multi-targeting drugs that are more cost-...
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Frontiers Media S.A.
2025-07-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2025.1631419/full |
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| author | Amin Aliabadi Amin Aliabadi Seyed Zachariah Moradi Sadaf Abdian Sajad Fakhri Javier Echeverría |
| author_facet | Amin Aliabadi Amin Aliabadi Seyed Zachariah Moradi Sadaf Abdian Sajad Fakhri Javier Echeverría |
| author_sort | Amin Aliabadi |
| collection | DOAJ |
| description | BackgroundCancer drug resistance significantly reduces the effectiveness of current anticancer treatments. Multiple dysregulated signaling pathways drive cancer initiation, progression, and related drug resistance. This highlights the need for developing new multi-targeting drugs that are more cost-effective, have fewer side effects, and remain effective against cancer. Drug repurposing offers a promising solution to expensive targeted therapies and helps overcome drug resistance. Mebendazole (MBZ), albendazole, flubendazole, and oxfendazole are broad-spectrum anti-helminthic drugs from the benzimidazole family.PurposeTherefore, MBZ demonstrated potential in suppressing the growth of various cancer cells, both in vitro and in vivo. Consequently, we thoroughly reviewed MBZ as a therapeutic option against cancer and related drug resistance.Results and discussionIn this study, we identified MBZ as a promising cancer treatment that works through multiple mechanisms such as regulating tumor angiogenesis, autophagy, and apoptosis, modulating key signaling pathways, boosting antitumor immune responses, and inhibiting matrix metalloproteinases activity—all of which are major factors in cancer drug resistance. Additionally, the development of new MBZ delivery systems aims to address its pharmacokinetic limitations. While the anticancer effects of MBZ are encouraging, further research is needed before it can be used clinically.ConclusionExtensive data from in vitro, in vivo, and clinical trials support MBZ’s anticancer potential and highlight the need for innovative delivery methods, including polymeric nanoparticles, nanostructured lipid formulations, micelles, nanosuspensions, and beyond. |
| format | Article |
| id | doaj-art-6042a01f201743f1ae9669cabe47ca88 |
| institution | DOAJ |
| issn | 1663-9812 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj-art-6042a01f201743f1ae9669cabe47ca882025-08-20T02:45:41ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122025-07-011610.3389/fphar.2025.16314191631419Critical dysregulated signaling pathways in drug resistance: highlighting the repositioning of mebendazole for cancer therapyAmin Aliabadi0Amin Aliabadi1Seyed Zachariah Moradi2Sadaf Abdian3Sajad Fakhri4Javier Echeverría5Department of Pharmacology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, IranStudent Research Committee, School of Medicine, Shiraz University of Medical Sciences, Shiraz, IranPharmaceutical Sciences Research Center, Health Institute, Kermanshah University of Medical Sciences, Kermanshah, IranStudent Research Committee, Kermanshah University of Medical Sciences, Kermanshah, IranPharmaceutical Sciences Research Center, Health Institute, Kermanshah University of Medical Sciences, Kermanshah, IranDepartamento de Ciencias del Ambiente, Facultad de Química y Biología, Universidad de Santiago de Chile, Santiago, ChileBackgroundCancer drug resistance significantly reduces the effectiveness of current anticancer treatments. Multiple dysregulated signaling pathways drive cancer initiation, progression, and related drug resistance. This highlights the need for developing new multi-targeting drugs that are more cost-effective, have fewer side effects, and remain effective against cancer. Drug repurposing offers a promising solution to expensive targeted therapies and helps overcome drug resistance. Mebendazole (MBZ), albendazole, flubendazole, and oxfendazole are broad-spectrum anti-helminthic drugs from the benzimidazole family.PurposeTherefore, MBZ demonstrated potential in suppressing the growth of various cancer cells, both in vitro and in vivo. Consequently, we thoroughly reviewed MBZ as a therapeutic option against cancer and related drug resistance.Results and discussionIn this study, we identified MBZ as a promising cancer treatment that works through multiple mechanisms such as regulating tumor angiogenesis, autophagy, and apoptosis, modulating key signaling pathways, boosting antitumor immune responses, and inhibiting matrix metalloproteinases activity—all of which are major factors in cancer drug resistance. Additionally, the development of new MBZ delivery systems aims to address its pharmacokinetic limitations. While the anticancer effects of MBZ are encouraging, further research is needed before it can be used clinically.ConclusionExtensive data from in vitro, in vivo, and clinical trials support MBZ’s anticancer potential and highlight the need for innovative delivery methods, including polymeric nanoparticles, nanostructured lipid formulations, micelles, nanosuspensions, and beyond.https://www.frontiersin.org/articles/10.3389/fphar.2025.1631419/fullmebendazolecancer drug resistancedrug repositioningangiogenesisapoptosissignaling pathways |
| spellingShingle | Amin Aliabadi Amin Aliabadi Seyed Zachariah Moradi Sadaf Abdian Sajad Fakhri Javier Echeverría Critical dysregulated signaling pathways in drug resistance: highlighting the repositioning of mebendazole for cancer therapy Frontiers in Pharmacology mebendazole cancer drug resistance drug repositioning angiogenesis apoptosis signaling pathways |
| title | Critical dysregulated signaling pathways in drug resistance: highlighting the repositioning of mebendazole for cancer therapy |
| title_full | Critical dysregulated signaling pathways in drug resistance: highlighting the repositioning of mebendazole for cancer therapy |
| title_fullStr | Critical dysregulated signaling pathways in drug resistance: highlighting the repositioning of mebendazole for cancer therapy |
| title_full_unstemmed | Critical dysregulated signaling pathways in drug resistance: highlighting the repositioning of mebendazole for cancer therapy |
| title_short | Critical dysregulated signaling pathways in drug resistance: highlighting the repositioning of mebendazole for cancer therapy |
| title_sort | critical dysregulated signaling pathways in drug resistance highlighting the repositioning of mebendazole for cancer therapy |
| topic | mebendazole cancer drug resistance drug repositioning angiogenesis apoptosis signaling pathways |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2025.1631419/full |
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