Chromosomal instability: A composite phenotype that influences sensitivity to chemotherapy

Chromosomal instability (CIN) is defined as continual gain or loss of whole chromosomes or fractions of chromosomes and is a major cause of the genomic instability that characterizes most solid tumors. CIN is associated with intrinsic resistance to taxanes, acquired multidrug resistance and poor pro...

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Bibliographic Details
Published in:Cell cycle (Georgetown, Tex.) Tex.), 2009-10, Vol.8 (20), p.3262-3266
Main Authors: McClelland, Sarah E., Burrell, Rebecca A., Swanton, Charles
Format: Article
Language:English
Subjects:
Antineoplastic Agents - pharmacology
Binding
Biology
Bioscience
Calcium
Cancer
Cell
Cell Line, Tumor
Chromosomal Instability
Chromosome Segregation
Cycle
Drug Resistance, Neoplasm
Humans
Kinetochores
Landes
Mitosis
Neoplasms - drug therapy
Organogenesis
Proteins
Taxoids - pharmacology
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Summary:Chromosomal instability (CIN) is defined as continual gain or loss of whole chromosomes or fractions of chromosomes and is a major cause of the genomic instability that characterizes most solid tumors. CIN is associated with intrinsic resistance to taxanes, acquired multidrug resistance and poor prognosis in many solid tumors, although recent evidence has shown that platinum agents, such as carboplatin, may specifically target CIN cancers.  The molecular basis for the increased genomic instability seen in CIN tumors and the mechanisms linking this instability to drug resistance are poorly understood, although some clues have been provided by recent work following live CIN cancer cells through multiple generations in the presence of anti-mitotic drugs. A common theme emerging from these studies is that CIN may be a multi-layered phenotype comprising (1) an increased propensity to missegregate chromosomes during mitosis and (2) a survival state specifically adapted to aneuploidy, frequent aberrant mitoses and the constant reshuffling of the genome. Identifying the molecular mechanisms underlying this composite CIN phenotype will be a key step forward in understanding drug resistance and the development of cancer in general, in addition to providing improved prognostic tools and therapeutic targets in CIN tumors.
ISSN:1538-4101
1551-4005
DOI:10.4161/cc.8.20.9690