Mebendazole Potentiates Radiation Therapy in Triple-Negative Breast Cancer

Zhang, Le; Dratver, Milana Bochkur; Yazal, Taha; Dong, Kevin; Nguyen, Andrea; Yu, Garrett; Dao, Amy; Dratver, Michael Bochkur; Duhachek-Muggy, Sara; Bhat, Kruttika; Alli, Claudia; Pajonk, Frank; Vlashi, Erina

doi:10.1016/j.ijrobp.2018.08.046

Cited by 53 publications

(49 citation statements)

References 53 publications

(68 reference statements)

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“…384 In addition, mebendazole was shown to have radio-sensitizing activity in breast cancer, and decreased the fraction of stem-like cells via the hedgehog pathway, probably regulating gliomaassociated oncogene homolog 1 (GLI1) (the downstream effector of the hedgehog pathway) to respond to DNA damage. [385][386][387] In further agreement, a recent study reported that mebendazole reduced GLI1 expression in advanced thyroid cancer. 388 Mebendazole was also shown to have anticancer activity and enhanced cisplatin-induced DNA damage, by inhibition of DNA doublestrand break repair, in head and neck squamous cell carcinoma.…”

Section: Non-oncology Drugs In Drug Repurposingsupporting

confidence: 64%

Overcoming cancer therapeutic bottleneck by drug repurposing

Zhang

Zhou

Xie

et al. 2020

Sig Transduct Target Ther

365

315

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Ever present hurdles for the discovery of new drugs for cancer therapy have necessitated the development of the alternative strategy of drug repurposing, the development of old drugs for new therapeutic purposes. This strategy with a cost-effective way offers a rare opportunity for the treatment of human neoplastic disease, facilitating rapid clinical translation. With an increased understanding of the hallmarks of cancer and the development of various data-driven approaches, drug repurposing further promotes the holistic productivity of drug discovery and reasonably focuses on target-defined antineoplastic compounds. The "treasure trove" of non-oncology drugs should not be ignored since they could target not only known but also hitherto unknown vulnerabilities of cancer. Indeed, different from targeted drugs, these old generic drugs, usually used in a multi-target strategy may bring benefit to patients. In this review, aiming to demonstrate the full potential of drug repurposing, we present various promising repurposed non-oncology drugs for clinical cancer management and classify these candidates into their proposed administration for either mono-or drug combination therapy. We also summarize approaches used for drug repurposing and discuss the main barriers to its uptake.

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Section: Non-oncology Drugs In Drug Repurposingsupporting

confidence: 64%

Overcoming cancer therapeutic bottleneck by drug repurposing

Zhang

Zhou

Xie

et al. 2020

Sig Transduct Target Ther

365

315

View full text Add to dashboard Cite

show abstract

“…Drug Treatment. TFP was identified as an inhibitor of radiation-induced phenotype conversion in a high-throughput screen described previously (22). After confirming tumor grafting via bioluminescent imaging, mice bearing GL261 tumors were injected i.p.…”

Section: Methodsmentioning

confidence: 99%

The dopamine receptor antagonist trifluoperazine prevents phenotype conversion and improves survival in mouse models of glioblastoma

Bhat

Saki

Vlashi

et al. 2020

Proc. Natl. Acad. Sci. U.S.A.

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Glioblastoma (GBM) is the deadliest adult brain cancer, and all patients ultimately succumb to the disease. Radiation therapy (RT) provides survival benefit of 6 mo over surgery alone, but these results have not improved in decades. We report that radiation induces a glioma-initiating cell phenotype, and we have identified trifluoperazine (TFP) as a compound that interferes with this phenotype conversion. TFP causes loss of radiation-induced Nanog mRNA expression, and activation of GSK3 with consecutive posttranslational reduction in p-Akt, Sox2, and β-catenin protein levels. TFP did not alter the intrinsic radiation sensitivity of glioma-initiating cells (GICs). Continuous treatment with TFP and a single dose of radiation reduced the number of GICs in vivo and prolonged survival in syngeneic and patient-derived orthotopic xenograft (PDOX) mouse models of GBM. Our findings suggest that the combination of a dopamine receptor antagonist with radiation enhances the efficacy of RT in GBM by preventing radiation-induced phenotype conversion of radiosensitive non-GICs into treatment-resistant, induced GICs (iGICs).

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“…Supplementary Table 1 ( 4 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 66 67 68 69 70 71 72 73 74 75 76 77 78 79 80 ) summarizes the antitumorigenicity of benzimidazole anthelmintics on cancer cell lines. Benzimidazole anthelmintics inhibit the progression of cancer through a variety of mechanisms.…”

Section: Antitumorigenic Effects Of Benzimidazole Anthelmintics In Camentioning

confidence: 99%

The Antitumor Potentials of Benzimidazole Anthelmintics as Repurposing Drugs

2020

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The development of refractory tumor cells limits therapeutic efficacy in cancer by activating mechanisms that promote cellular proliferation, migration, invasion, metastasis, and survival. Benzimidazole anthelmintics have broad-spectrum action to remove parasites both in human and veterinary medicine. In addition to being antiparasitic agents, benzimidazole anthelmintics are known to exert anticancer activities, such as the disruption of microtubule polymerization, the induction of apoptosis, cell cycle (G2/M) arrest, anti-angiogenesis, and blockage of glucose transport. These antitumorigenic effects even extend to cancer cells resistant to approved therapies and when in combination with conventional therapeutics, enhance anticancer efficacy and hold promise as adjuvants. Above all, these anthelmintics may offer a broad, safe spectrum to treat cancer, as demonstrated by their long history of use as antiparasitic agents. The present review summarizes central literature regarding the anticancer effects of benzimidazole anthelmintics, including albendazole, parbendazole, fenbendazole, mebendazole, oxibendazole, oxfendazole, ricobendazole, and flubendazole in cancer cell lines, animal tumor models, and clinical trials. This review provides valuable information on how to improve the quality of life in patients with cancers by increasing the treatment options and decreasing side effects from conventional therapy.

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Mebendazole Potentiates Radiation Therapy in Triple-Negative Breast Cancer

Abstract: The data presented in this study support the repurposing of mebendazole as a combination treatment with radiation therapy in TNBC patients.

Cited by 53 publications

References 53 publications

Overcoming cancer therapeutic bottleneck by drug repurposing

Overcoming cancer therapeutic bottleneck by drug repurposing

The dopamine receptor antagonist trifluoperazine prevents phenotype conversion and improves survival in mouse models of glioblastoma

The Antitumor Potentials of Benzimidazole Anthelmintics as Repurposing Drugs

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