Preclinical evaluation of the nutlin molecule RG7112 in neuroblastoma

01 January 2013 → 31 December 2015
Research Foundation - Flanders (FWO)
Research disciplines
  • Medical and health sciences
    • Pediatrics and neonatology
    • Pediatrics and neonatology
    • Nursing
    • Pediatrics and neonatology
Project description

Neuroblastoma (NB) is an aggressive and often fatal childhood cancer for which new therapeutic strategies are clearly needed. An attractive option for molecular cancer therapy may consist of targeted reactivation of the p53 tumor suppressor protein, which is only rarely mutated in NB. Nutlins are a class of small molecules that selectively inhibit the interaction between p53 and its negative regulator MDM2. This results in activation of the p53 pathway and potent antitumor effects on condition that p53 is wild-type. One of the nutlin compounds, RG7112, has progressed to phase I clinical trials for several types of adult cancer. The goal of this research project is to preclinically evaluate the potential therapeutic utility of RG7112 for the treatment of NB. More specifically, we will investigate the antitumor effects of RG7112 monotherapy in NB cells, we will try to identify other targeted drugs that result in enhanced therapeutic effects against NB cells when they are combined with RG7112, and we will examine whether serum microRNAs (miRNAs) are useful biomarkers of the response to RG7112 treatment in mouse models of NB. If successful, these research efforts may lead to the design and initiation of a phase I clinical trial of RG7112 in patients with relapsed/refractory NB.