| Title |
Repurposing Mebendazole as a Replacement for Vincristine for the Treatment of Brain Tumors
|
|---|---|
| Published in |
Molecular Medicine, April 2017
|
| DOI | 10.2119/molmed.2017.00011 |
| Pubmed ID | |
| Authors |
Michelle De Witt, Alexander Gamble, Derek Hanson, Daniel Markowitz, Caitlin Powell, Saleh Al Dimassi, Mark Atlas, John Boockvar, Rosamaria Ruggieri, Marc Symons |
| Abstract |
The microtubule inhibitor vincristine is currently used to treat a variety of brain tumors, including low-grade glioma and anaplastic oligodendroglioma. Vincristine, however, does not penetrate well into brain tumor tissue, and moreover, it displays dose-limiting toxicities, including peripheral neuropathy. Mebendazole, a Food and Drug Administration-approved anthelmintic drug with a favorable safety profile, has recently been shown to display strong therapeutic efficacy in animal models of both glioma and medulloblastoma. Importantly, appropriate formulations of mebendazole yield therapeutically effective concentrations in the brain. Mebendazole has been shown to inhibit microtubule formation, but it is not known whether its potency against tumor cells is mediated by this inhibitory effect. To investigate this, we examined the effects of mebendazole on GL261 glioblastoma cell viability, microtubule polymerization and metaphase arrest, and found that the effective concentrations to inhibit these functions are very similar. In addition, using mebendazole as a seed for the National Cancer Institute (NCI) COMPARE program revealed that the top-scoring drugs were highly enriched in microtubule-targeting drugs. Taken together, these results indicate that the cell toxicity of mebendazole is indeed caused by inhibiting microtubule formation. We also compared the therapeutic efficacy of mebendazole and vincristine against GL261 orthotopic tumors. We found that mebendazole showed a significant increase in animal survival time, whereas vincristine, even at a dose close to its maximum tolerated dose, failed to show any efficacy. In conclusion, our results strongly support the clinical use of mebendazole as a replacement for vincristine for the treatment of brain tumors. |
X Demographics
The data shown below were collected from the profiles of 3 X users who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Australia | 2 | 67% |
| Unknown | 1 | 33% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 3 | 100% |
Mendeley readers
The data shown below were compiled from readership statistics for 79 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 79 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Ph. D. Student | 10 | 13% |
| Student > Master | 9 | 11% |
| Researcher | 8 | 10% |
| Student > Bachelor | 6 | 8% |
| Student > Doctoral Student | 4 | 5% |
| Other | 12 | 15% |
| Unknown | 30 | 38% |
| Readers by discipline | Count | As % |
|---|---|---|
| Pharmacology, Toxicology and Pharmaceutical Science | 12 | 15% |
| Medicine and Dentistry | 11 | 14% |
| Chemistry | 7 | 9% |
| Agricultural and Biological Sciences | 4 | 5% |
| Unspecified | 3 | 4% |
| Other | 8 | 10% |
| Unknown | 34 | 43% |
Attention Score in Context
This research output has an Altmetric Attention Score of 29. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 04 December 2023.
All research outputs
#1,288,698
of 24,937,289 outputs
Outputs from Molecular Medicine
#35
of 1,249 outputs
Outputs of similar age
#25,541
of 314,932 outputs
Outputs of similar age from Molecular Medicine
#1
of 3 outputs
Altmetric has tracked 24,937,289 research outputs across all sources so far. Compared to these this one has done particularly well and is in the 94th percentile: it's in the top 10% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 1,249 research outputs from this source. They typically receive more attention than average, with a mean Attention Score of 8.3. This one has done particularly well, scoring higher than 97% of its peers.
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