Journal
JOURNAL OF CELLULAR BIOCHEMISTRY
Volume 111, Issue 4, Pages 782-790Publisher
WILEY
DOI: 10.1002/jcb.22781
Keywords
CHROMOSOMAL INSTABILITY; HER2; BREAST CANCER; DRUG RESISTANCE; TUMOUR HETEROGENEITY; MICROTUBULE; CEP17
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Funding
- MRC
- CR-UK
- National Institute of Health [NCI SPORE P50 CA 89393, R21LM008823-01A1]
- Danish Council for Independent Research-Medical Sciences (FSS)
- Breast Cancer Research Foundation (BCRF)
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Chromosomal instability (CIN) is a common cause of tumour heterogeneity and poor prognosis in solid tumours and describes cell-cell variation in chromosome structure or number across a tumour population. In this article we consider evidence suggesting that CIN may be targeted and may influence response to distinct chemotherapy regimens, using HER2-positive breast cancer as an example. Pre-clinical models have indicated a role for HER2 signalling in initiating CIN and defective cell-cycle control, and evidence suggests that HER2-targeting may attenuate this process. Anthracyclines and platinum agents may target tumours with distinct patterns of karyotypic complexity, whereas taxanes may have preferential activity in tumours with relative chromosomal stability. A greater understanding of karyotypic complexity and identification of methods to directly examine and target CIN may support novel strategies to improve outcome in cancer. J. Cell. Biochem. 111: 782-790, 2010. (C) 2010 Wiley-Liss, Inc.
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