Published July 24, 2013 | Version v1
Journal article Metadata-only

Characterization of a Dual CDC7/CDK9 Inhibitor in Multiple Myeloma Cellular Models

Creators

  • 1. Centre for Chromosome Biology, School of Natural Sciences National University of Ireland Galway, Galway (Ireland)
  • 2. Department of Haematology, Galway University Hospital, Galway (Ireland)
  • 3. Department of Medicine, National University of Ireland Galway, Galway (Ireland)
  • 4. Nerviano Medical Sciences S.r.l., Via Pasteur 10, Nerviano 20014 (Italy)

Description

Two key features of myeloma cells are the deregulation of the cell cycle and the dependency on the expression of the BCL2 family of anti-apoptotic proteins. The cell division cycle 7 (CDC7) is an essential S-phase kinase and emerging CDC7 inhibitors are effective in a variety of preclinical cancer models. These compounds also inhibit CDK9 which is relevant for MCL-1 expression. The activity and mechanism of action of the dual CDC7/CDK9 inhibitor PHA-767491 was assessed in a panel of multiple myeloma cell lines, in primary samples from patients, in the presence of stromal cells and in combination with drugs used in current chemotherapeutic regimens. We report that in all conditions myeloma cells undergo cell death upon PHA-767491 treatment and we report an overall additive effect with melphalan, bortezomib and doxorubicin, thus supporting further assessment of targeting CDC7 and CDK9 in multiple myeloma

Availability note (English)

Available from http://dx.doi.org/10.3390/cancers5030901; Available from http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3795371

Additional details

Identifiers

URL
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3795371;
DOI
10.3390/cancers5030901;

Publishing Information

Journal Title
Cancers (Basel)
Journal Volume
5
Journal Issue
3
Journal Page Range
p. 901-918
ISSN
2072-6694

INIS

Country of Publication
Switzerland
Country of Input or Organization
International Atomic Energy Agency (IAEA)
INIS RN
47001842
Subject category
S60: APPLIED LIFE SCIENCES; S62: RADIOLOGY AND NUCLEAR MEDICINE;
Descriptors DEI
APOPTOSIS; CELL CYCLE; CELL DIVISION; CHARGES; DNA REPLICATION; NEOPLASMS
Descriptors DEC
DISEASES; NUCLEIC ACID REPLICATION

Optional Information

Copyright
Copyright (c) 2013 by the authors
Notes
PMCID: PMC3795371; PMID: 24202326; PUBLISHER-ID: cancers-05-00901; OAI: oai:pubmedcentral.nih.gov:3795371; licensee MDPI, Basel, Switzerland.; This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/3.0/).