Russo, Roberta ORCID: 0000-0002-3624-7721, Cimmino, Flora ORCID: 0000-0003-1538-9285, Pezone, Lucia, Manna, Francesco ORCID: 0000-0003-1710-6680, Avitabile, Marianna ORCID: 0000-0002-5352-6503, Langella, Concetta, Koster, Jan ORCID: 0000-0002-0890-7585, Casale, Fiorina, Raia, Maddalena, Viola, Giampietro ORCID: 0000-0001-9329-165X, Fischer, Matthias, Iolascon, Achille and Capasso, Mario ORCID: 0000-0003-3306-1259 (2017). Kinome expression profiling of human neuroblastoma tumors identifies potential drug targets for ultra high-risk patients. Carcinogenesis, 38 (10). S. 1011 - 1021. OXFORD: OXFORD UNIV PRESS. ISSN 1460-2180

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Abstract

Neuroblastoma (NBL) accounts for >7% of malignancies in patients younger than 15 years. Low-and intermediate-risk patients exhibit excellent or good prognosis after treatment, whereas for high-risk (HR) patients, the estimated 5-year survival rates is still <40%. The ability to stratify HR patients that will not respond to standard treatment strategies is critical for informed treatment decisions. In this study, we have generated a specific kinome gene signature, named Kinome-27, which is able to identify a subset of HR-NBL tumors, named ultra-HR NBL, with highly aggressive clinical behavior that not adequately respond to standard treatments. We have demonstrated that NBL cell lines expressing the same kinome signature of ultra-HR tumors (ultra-HR-like cell lines) may be selectively targeted by the use of two drugs [suberoylanilide hydroxamic acid (SAHA) and Radicicol], and that the synergic combination of these drugs is able to block the ultra-HR-like cells in G2/M phase of cell cycle. The use of our signature in clinical practice will allow identifying patients with negative outcome, which would benefit from new and more personalized treatments. Preclinical in vivo studies are needed to consolidate the SAHA and Radicicol treatment in ultra-HR NBL patients.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Russo, RobertaUNSPECIFIEDorcid.org/0000-0002-3624-7721UNSPECIFIED
Cimmino, FloraUNSPECIFIEDorcid.org/0000-0003-1538-9285UNSPECIFIED
Pezone, LuciaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Manna, FrancescoUNSPECIFIEDorcid.org/0000-0003-1710-6680UNSPECIFIED
Avitabile, MariannaUNSPECIFIEDorcid.org/0000-0002-5352-6503UNSPECIFIED
Langella, ConcettaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Koster, JanUNSPECIFIEDorcid.org/0000-0002-0890-7585UNSPECIFIED
Casale, FiorinaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Raia, MaddalenaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Viola, GiampietroUNSPECIFIEDorcid.org/0000-0001-9329-165XUNSPECIFIED
Fischer, MatthiasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Iolascon, AchilleUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Capasso, MarioUNSPECIFIEDorcid.org/0000-0003-3306-1259UNSPECIFIED
URN: urn:nbn:de:hbz:38-215243
DOI: 10.1093/carcin/bgx077
Journal or Publication Title: Carcinogenesis
Volume: 38
Number: 10
Page Range: S. 1011 - 1021
Date: 2017
Publisher: OXFORD UNIV PRESS
Place of Publication: OXFORD
ISSN: 1460-2180
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
RETINOIC ACID; CELLS; CLASSIFICATION; COMBINATION; VORINOSTAT; INHIBITORS; STRATEGIES; APOPTOSIS; CHILDREN; THERAPYMultiple languages
OncologyMultiple languages
Refereed: Yes
URI: http://kups.ub.uni-koeln.de/id/eprint/21524

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