DNA Damage Response Inhibitor Combinations Exert Synergistic Antitumor Activity in Aggressive B-Cell Lymphomas.


Journal

Molecular cancer therapeutics
ISSN: 1538-8514
Titre abrégé: Mol Cancer Ther
Pays: United States
ID NLM: 101132535

Informations de publication

Date de publication:
07 2019
Historique:
received: 13 08 2018
revised: 20 12 2018
accepted: 02 05 2019
pubmed: 9 5 2019
medline: 24 6 2020
entrez: 9 5 2019
Statut: ppublish

Résumé

The DNA damage response (DDR) kinases ATR, Chk1, and Wee1 play vital roles in the response to replication stress and in maintaining cancer genomic stability. Inhibitors of these kinases are currently under clinical investigation. Mantle cell lymphoma (MCL) and diffuse large B-cell lymphoma (DLBCL) are aggressive lymphomas whose clinical outcome is still largely unsatisfactory. These cell lymphoma subtypes are highly dependent on both Chk1 and Wee1 for survival. We investigated the activity of the ATR inhibitor AZD6738 as single agent and in combination with either Chk1 (AZD6738) or Wee1 (AZD1775) inhibitors in several preclinical models of MCL and DLBCL. This study included preclinical

Identifiants

pubmed: 31064869
pii: 1535-7163.MCT-18-0919
doi: 10.1158/1535-7163.MCT-18-0919
doi:

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

1255-1264

Informations de copyright

©2019 American Association for Cancer Research.

Auteurs

Valentina Restelli (V)

Laboratory of Molecular Pharmacology and Laboratory of Cancer Pharmacology, Department of Oncology, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Milan, Italy.

Monica Lupi (M)

Laboratory of Molecular Pharmacology and Laboratory of Cancer Pharmacology, Department of Oncology, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Milan, Italy.

Rosaria Chilà (R)

Laboratory of Molecular Pharmacology and Laboratory of Cancer Pharmacology, Department of Oncology, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Milan, Italy.

Micaela Vagni (M)

Laboratory of Molecular Pharmacology and Laboratory of Cancer Pharmacology, Department of Oncology, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Milan, Italy.

Chiara Tarantelli (C)

Institute of Oncology Research (IOR), Università della Svizzera Italiana (USI), Bellinzona, Switzerland.

Filippo Spriano (F)

Institute of Oncology Research (IOR), Università della Svizzera Italiana (USI), Bellinzona, Switzerland.

Eugenio Gaudio (E)

Institute of Oncology Research (IOR), Università della Svizzera Italiana (USI), Bellinzona, Switzerland.

Francesco Bertoni (F)

Institute of Oncology Research (IOR), Università della Svizzera Italiana (USI), Bellinzona, Switzerland.

Giovanna Damia (G)

Laboratory of Molecular Pharmacology and Laboratory of Cancer Pharmacology, Department of Oncology, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Milan, Italy. giovanna.damia@marionegri.it laura.carrassa@marionegri.it.

Laura Carrassa (L)

Laboratory of Molecular Pharmacology and Laboratory of Cancer Pharmacology, Department of Oncology, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Milan, Italy. giovanna.damia@marionegri.it laura.carrassa@marionegri.it.

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Classifications MeSH