More on propranolol and neuroblastoma

Two recent studies published in the Journal of Pediatric Surgery and in Oncotarget have confirmed our work on the potential role of betablocker (Pasquier and al. Br J Cancer 2013) in the treatment of neuroblastoma.

Indeed, Xu T and al. from the Department of Surgery of Children’s Hospital, Fudan University, Shanghai, China have just published an article entitled : anti-angiogenic effect of propranolol on the growth of the neuroblastoma xenografts in nude mice in the Journal of Pediatric Surgery. Using neuroblastoma xenografts models, they show that daily propranolol 2, 5 and 10 mg/kg/d can inhibit tumour growth in a dose dependent manner which was associated with a decrease in tumor microvessel density and in VEGF, MMP2 and MMP9 strongly suggersting an antiangiogenic effect.

Elsewhere, Wolter and al. from the University of Toronto and Hospital for Sick Children in Toronto, Canada, reported in Oncotarget an article entitled : Anti-tumor activity of the beta-adrenergic receptor antagonist propranolol in neuroblastoma. They show that propranolol inhibited the growth of a panel of fifteen NB cell lines irrespective of MYCN status and also induced apoptosis. Exploring the mechanism of action of propranolol they showed that antitumoral activity was dependent on inhibition of the β2, and not β1 adrenergic receptor, and that treatment resulted in activation of p53 and p73 signaling in vitro. Interestingly, higher mRNA levels of β2 adrenergic receptor correlate with improved patient survival and in vivo, in neuroblastoma xenografts, propranolol lead to a slower tumour growth as weel as as a prolonged survival. Propranolol was also synergistic with topoisomerase inhibitor and cox-inhibitor.

Taken together, the 3 published studies pave the way for the introduction of propranol in patients with relapsing or refractory neuroblastome alone or in combination with topoisomerase, vinca-alkaloids or other reposition drug such as celecoxib. Such combinations could be easily used in children living both in LMIC and HIC.

1) Pasquier E, Street J, Pouchy C, Carre M, Gifford AJ, Murray J, Norris MD, Trahair T, Andre N, Kavallaris M. β-blockers increase response to chemotherapy via direct antitumour and anti-angiogenic mechanisms in neuroblastoma. Br J Cancer. 2013 Jun 25;108(12):2485-94.

2) Xu T, Xiao X, Zheng S, Zheng J, Zhu H, Ji Y, Yang SJ Pediatr Surg. 2013 Dec;48(12):2460-5. Antiangiogenic effect of propranolol on the growth of the neuroblastoma xenografts in nude mice.

3) Jennifer K Wolter, Nikolaus E Wolter, Alvaro Blanch, Teresa Partridge, Lynn Cheng, Daniel A. Morgenstern, Monika Podkowa, David R. Kaplan, and Meredith S. Irwin Anti-tumor activity of the beta-adrenergic receptor antagonist propranolol in neuroblastome. Oncotarget advanced publication