Vinblastine and antihelmintic mebendazole potentiate temozolomide in resistant gliomas
- 1 April 2018
- journal article
- research article
- Published by Springer Science and Business Media LLC in Investigational New Drugs
- Vol. 36 (2), 323-331
- https://doi.org/10.1007/s10637-017-0503-7
Abstract
Glioblastoma (GBM) is a very aggressive tumor that has not had substantial therapeutic improvement since the introduction of temozolomide (TMZ) in combination with radiotherapy. Combining TMZ with other chemotherapeutic agents is a strategy that could be further explored for GBM. To search for molecular predictors of TMZ resistance, the TCGA (The Cancer Genome Atlas) database was utilized to assess the impact of specific genes on TMZ response. Patients whose tumors expressed low levels of FGFR3 and AKT2 responded poorly to TMZ. Combination treatment of vinblastine (VBL) plus mebendazole (MBZ) with TMZ was more effective in reducing cell number in most cultures when compared to TMZ alone, especially in cells with low expression levels of FGFR3 and AKT2. Cell cycle distribution and nuclear morphometric analysis indicated that the triple combination of TMZ, VBL and MBZ (TVM) was able to induce polyploidy and senescence, in addition to increasing the Notch3 RNA level in patient-derived gliomas. Thus, this set of data suggests that the triple combination of TMZ, VBL and MBZ may be a considerable therapeutic alternative for the TMZ-tolerant gliomas that harbor low expression of FGFR3/AKT2.Funding Information
- Fundação de Amparo à Pesquisa do Estado do Rio Grande do Sul (PPSUS 1210-2551/13-1, PRONEX 16/2551)
- Conselho Nacional de Desenvolvimento Científico e Tecnológico (Universal 458139/2014-9)
This publication has 37 references indexed in Scilit:
- XIAP downregulation accompanies mebendazole growth inhibition in melanoma xenograftsAnti-Cancer Drugs, 2013
- Adjuvant Procarbazine, Lomustine, and Vincristine Chemotherapy in Newly Diagnosed Anaplastic Oligodendroglioma: Long-Term Follow-Up of EORTC Brain Tumor Group Study 26951Journal of Clinical Oncology, 2013
- Nuclear Morphometric Analysis (NMA): Screening of Senescence, Apoptosis and Nuclear IrregularitiesPLOS ONE, 2012
- A phase II study of O6-benzylguanine and temozolomide in pediatric patients with recurrent or progressive high-grade gliomas and brainstem gliomas: a Pediatric Brain Tumor Consortium studyJournal of Neuro-Oncology, 2011
- Antiparasitic mebendazole shows survival benefit in 2 preclinical models of glioblastoma multiformeNeuro-Oncology, 2011
- Molecular targeting of glioblastoma: Drug discovery and therapiesTrends in Molecular Medicine, 2011
- Temozolomide Versus Procarbazine, Lomustine, and Vincristine in Recurrent High-Grade GliomaJournal of Clinical Oncology, 2010
- Connexin 32 potentiates vinblastine‐induced cytotoxicity in renal cell carcinoma cellsMolecular Carcinogenesis, 2006
- Radiotherapy plus Concomitant and Adjuvant Temozolomide for GlioblastomaNew England Journal of Medicine, 2005
- Penetration of intra-arterially administered vincristine in experimental brain tumorNeuro-Oncology, 2004