| Nutlins and ionizing radiation in cancer therapy. | |
| | |
MedLine Citation:
|
PMID: 20166982 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
Radioresistance stands as a fundamental barrier that limits the effectiveness of radiotherapy in cancer treatment. Recent evidences suggest that radioresistance is due to tumour repopulation and involves several signalling pathways, including p53/MDM2 interaction. Ionizing radiation induces p53-dependent MDM2 gene transcription that, in turn, inhibits p53 transcriptional activity, favouring its nuclear export and stimulating its degradation. In light of the observation that in many human tumours the inadequate function of p53 is the result of MDM2 over-expression, several authors have considered as an attractive therapeutic strategy to activate p53 signalling in tumours by inhibiting MDM2 activities or p53/MDM2 interaction. We retain that, by preventing the interaction p53/MDM2 with Nutlin, a small molecule that bind at the interface between these two proteins, the effectiveness of ionizing radiation treatment could be improved. Promising results have recently emerged from in vitro studies performed on laryngeal, prostate and lung cancer cell lines treated with Nutlin in combination with ionizing radiation. Based on these findings, we believe that the combined approach Nutlin/ionizing radiation should be further investigated for efficacy on both solid tumours and lymphoproliferative disorders as well as for side effects on normal cells and tissues. Therefore, the purpose of this review is to report the first results obtained by using Nutlins alone or in combination with other therapeutic agents on primary tumour cells, in vitro cell lines or tumour xenografts and to present the most recent advances in the understanding of the molecular mechanisms underlining ionizing radiation cytotoxicity and resistance. |
| | |
Authors:
|
Gianna Impicciatore; Silvia Sancilio; Sebastiano Miscia; Roberta Di Pietro |
Publication Detail:
|
Type: Journal Article; Research Support, Non-U.S. Gov't; Review |
Journal Detail:
|
Title: Current pharmaceutical design Volume: 16 ISSN: 1873-4286 ISO Abbreviation: Curr. Pharm. Des. Publication Date: 2010 |
Date Detail:
|
Created Date: 2010-05-27 Completed Date: 2010-08-20 Revised Date: - |
Medline Journal Info:
|
Nlm Unique ID: 9602487 Medline TA: Curr Pharm Des Country: Netherlands |
Other Details:
|
Languages: eng Pagination: 1427-42 Citation Subset: IM |
Affiliation:
|
Dipartimento di Biomorfologia, Università G. d'Annunzio Chieti-Pescara, Via dei Vestini, 31, 66100 Chieti (CH), Italy. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Animals Antineoplastic Agents / administration & dosage, pharmacology, therapeutic use* Apoptosis / drug effects, radiation effects Cell Line, Tumor Combined Modality Therapy Humans Imidazoles / administration & dosage, pharmacology, therapeutic use* Neoplasms / drug therapy*, metabolism, pathology, radiotherapy* Piperazines / administration & dosage, pharmacology, therapeutic use* Proto-Oncogene Proteins c-mdm2 / antagonists & inhibitors Radiation, Ionizing Tumor Suppressor Protein p53 / metabolism |
| Chemical | |
Reg. No./Substance:
|
0/Antineoplastic Agents; 0/Imidazoles; 0/Piperazines; 0/Tumor Suppressor Protein p53; 0/nutlin 3; EC 6.3.2.19/Proto-Oncogene Proteins c-mdm2 |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Most Efficient Routes for the Synthesis of Diamino Acid-Derived Compounds.
Next Document: Cell Cycle as a Target of Antineoplastic Drugs.