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Kinome expression profiling of human neuroblastoma tumors identifies potential drug targets for ultra high-risk patients.
Russo, Roberta; Cimmino, Flora; Pezone, Lucia; Manna, Francesco; Avitabile, Marianna; Langella, Concetta; Koster, Jan; Casale, Fiorina; Raia, Maddalena; Viola, Giampietro; Fischer, Matthias; Iolascon, Achille; Capasso, Mario.
Afiliação
  • Russo R; Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Università degli Studi di Napoli Federico II, Napoli, Italy.
  • Cimmino F; CEINGE Biotecnologie Avanzate, Napoli, Italy.
  • Pezone L; Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Università degli Studi di Napoli Federico II, Napoli, Italy.
  • Manna F; CEINGE Biotecnologie Avanzate, Napoli, Italy.
  • Avitabile M; CEINGE Biotecnologie Avanzate, Napoli, Italy.
  • Langella C; Department of Medicine, University of Verona.
  • Koster J; Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Università degli Studi di Napoli Federico II, Napoli, Italy.
  • Casale F; CEINGE Biotecnologie Avanzate, Napoli, Italy.
  • Raia M; Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Università degli Studi di Napoli Federico II, Napoli, Italy.
  • Viola G; CEINGE Biotecnologie Avanzate, Napoli, Italy.
  • Fischer M; Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Università degli Studi di Napoli Federico II, Napoli, Italy.
  • Iolascon A; CEINGE Biotecnologie Avanzate, Napoli, Italy.
  • Capasso M; Department of Oncogenomics, Academic Medical Center, University of Amsterdam, Meibergdreef, Amsterdam, The Netherlands.
Carcinogenesis ; 38(10): 1011-1020, 2017 10 01.
Article em En | MEDLINE | ID: mdl-28968651
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.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Fosfotransferases / Terapia de Alvo Molecular / Neuroblastoma / Antineoplásicos Tipo de estudo: Etiology_studies / Prognostic_studies / Risk_factors_studies Limite: Humans Idioma: En Revista: Carcinogenesis Ano de publicação: 2017 Tipo de documento: Article País de afiliação: Itália

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Fosfotransferases / Terapia de Alvo Molecular / Neuroblastoma / Antineoplásicos Tipo de estudo: Etiology_studies / Prognostic_studies / Risk_factors_studies Limite: Humans Idioma: En Revista: Carcinogenesis Ano de publicação: 2017 Tipo de documento: Article País de afiliação: Itália