Paola Secchiero, Raffaella Bosco, Claudio Celeghini and Giorgio Zauli Pages 569 - 577 ( 9 )
Nutlin-3 is a small molecule inhibitor of the MDM2/p53 interaction, which leads to the non-genotoxic p53 stabilization, activation of cell cycle arrest and apoptosis pathways. A series of recent studies have strengthened the concept that selective, non-genotoxic p53 activation by Nutlin-3 might represent an alternative to the current cytotoxic chemotherapy, in particular for pediatric tumors and for hematological malignancies, which retain a high percentage of p53wild-type status at diagnosis. Like most other drugs employed in cancer therapy, it will be unlikely that Nutlin-3 will be used as a monotherapy. In this respect, Nutlin-3 shows a synergistic cytotoxic effect when used in combination with innovative drugs, such as TRAIL or bortozemib. Although Nutlin-3 is currently in phase I clinical trial for the treatment of retinoblastoma, its effects on normal tissues and cell types remain largely to be determined and will require further investigation in the future years.
Pediatric malignancies,hematological malignancies,p53 pathway,apoptosis,senescence,therapeutic combinations,Nutlin-3,MDM2,HDM2,PEDIATRIC TUMORS,chemotherapy,malignancies,P-gp,p53-independent,leukemia,synergistic,endothelial,autophagic,pharmacokinetics
, , , Institute for Maternal and Child Health, IRCCS Burlo Garofolo, Via dell'Istria 65/1, 34137 Trieste, Italy.