Recent advances in the therapeutic perspectives of nutlin-3

Paola Secchiero, Raffaella Bosco, Claudio Celeghini, Giorgio Zauli

Research output: Contribution to journalArticlepeer-review


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 p53 wild-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.

Original languageEnglish
Pages (from-to)569-577
Number of pages9
JournalCurrent Pharmaceutical Design
Issue number6
Publication statusPublished - Feb 2011


  • Apoptosis
  • Hematological malignancies
  • P53 pathway
  • Pediatric malignancies
  • Senescence
  • Therapeutic combinations

ASJC Scopus subject areas

  • Drug Discovery
  • Pharmacology


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