Abstract
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.
Keywords: 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
Current Pharmaceutical Design
Title: Recent Advances in the Therapeutic Perspectives of Nutlin-3
Volume: 17 Issue: 6
Author(s): Paola Secchiero, Raffaella Bosco, Claudio Celeghini and Giorgio Zauli
Affiliation:
Keywords: 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
Abstract: 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.
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Cite this article as:
Secchiero Paola, Bosco Raffaella, Celeghini Claudio and Zauli Giorgio, Recent Advances in the Therapeutic Perspectives of Nutlin-3, Current Pharmaceutical Design 2011; 17 (6) . https://dx.doi.org/10.2174/138161211795222586
DOI https://dx.doi.org/10.2174/138161211795222586 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
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