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β-blockers increase response to chemotherapy via direct antitumour and anti-angiogenic mechanisms in neuroblastoma.

A joint work of researcher from the Children’s Cancer Institute Australia, the Centre de Recherche en Oncologie biologique et Oncopharmacologie, Aix-Marseille University the Department of Hematology and Pediatric Oncology, La Timone University Hospital of Marseille and MGHI entitled β-blockers increase response to chemotherapy via direct antitumour and anti-angiogenic mechanisms in neuroblastoma has been published in the British Journal of Cancer. It reports on the use of drug repositioning of β-blockers to increase treatment efficacy against neuroblastoma. Indeed, their combination with chemotherapy proved to be beneficial for the treatment of this disease and may be other drug-refractory cancers.

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Pasquier E, Street J, Pouchy C, Carre M, Gifford AJ, Murray J, Norris MD, Trahair T, Andre N, Kavallaris M. Br J Cancer. 2013 May 21 Epub ahead of print


Background:The use of for the management of hypertension has been recently associated with significant cliβ-blockersnical benefits in cancer patients. Herein, we investigated whether β-blockers could be used in combination with chemotherapy for the treatment of neuroblastoma. Methods:Seven β-blockers were tested for their antiproliferative and anti-angiogenic properties alone, and in combination with chemotherapy in vitro; the most potent drug combinations were evaluated in vivo in the TH-MYCN mouse model of neuroblastoma. Results:Three β-blockers (i.e., carvedilol, nebivolol and propranolol) exhibited potent anticancer properties in vitro and interacted synergistically with vincristine, independently of P-glycoprotein expression. β-blockers potentiated the anti-angiogenic, antimitochondrial, antimitotic and ultimately pro-apoptotic effects of vincristine. In vivo, β-blockers alone transiently slowed tumour growth as compared with vehicle only (P<0.01). More importantly, when used in combination, β-blockers significantly increased the tumour regression induced by vincristine (P<0.05). This effect was associated with an increase in tumour angiogenesis inhibition (P<0.001) and ultimately resulted in a four-fold increase in median survival, as compared with vincristine alone (P<0.01). Conclusion:β-blockers can increase treatment efficacy against neuroblastoma, and their combination with chemotherapy may prove beneficial for the treatment of this disease and other drug-refractory cancers.