Combined targeting of the p53 and pRb pathway in neuroblastoma does not lead to synergistic responses

Despite intensive treatment protocols and recent advances, neuroblastomas still account for approximately 15% of all childhood cancer deaths. In contrast with adult cancers, p53 pathway inactivation in neuroblastomas is rarely caused by p53 mutation  but rather by altered MDM2 or p14ARF expression. Moreover, neuroblastomas are characterised by high proliferation rates, frequently triggered by pRb pathway dysfunction due to aberrant expression of cyclin D1, CDK4 or p16INK4a. Simultaneous disturbance of these pathways can occur via co-amplificat ion of MDM2 and CDK4 or homozygous deletion of CDKN2A, which encodes both p14ARF and p16INK4a.

Source: European Journal of Cancer - November 12, 2020 Category: Cancer & Oncology Authors: Nil A. Schubert, Linda Schild, Stijn van Oirschot, Kaylee M. Keller, Lindy K. Alles, Lindy Vernooij, Marloes E. Nulle, M. Emmy M. Dolman, Marlinde L. van den Boogaard, Jan J. Molenaar Tags: Original Research Source Type: research