Journal of Cellular Biochemistry

Targeting chromosomal instability and tumour heterogeneity in HER2-positive breast cancer

Authors

  • Rebecca A. Burrell,

    1. Translational Cancer Therapeutics Laboratory, London Research Institute, 44 Lincoln's Inn Fields, London WC2A 3PX, UK
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  • Nicolai Juul,

    1. Center for Biological Sequence Analysis, Technical University of Denmark, DK 2800 Lyngby, Denmark
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  • Stephen R. Johnston,

    1. Department of Medicine, Breast Unit, Royal Marsden Hospital, Downs Road, Sutton SM2 5PT, UK
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  • Jorge S. Reis-Filho,

    1. The Breakthrough Breast Cancer Research Centre, Institute of Cancer Research, London, UK
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  • Zoltan Szallasi,

    1. Center for Biological Sequence Analysis, Technical University of Denmark, DK 2800 Lyngby, Denmark
    2. Children's Hospital Informatics Program at the Harvard-MIT Division of Health, Sciences and Technology (CHIP@HST), Harvard Medical School, Boston, Massachusetts 02115
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  • Charles Swanton

    Corresponding author
    1. Translational Cancer Therapeutics Laboratory, London Research Institute, 44 Lincoln's Inn Fields, London WC2A 3PX, UK
    2. Department of Medicine, Breast Unit, Royal Marsden Hospital, Downs Road, Sutton SM2 5PT, UK
    • 44 Lincoln's Inn Fields, London WC2A3PX, UK.
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Abstract

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. © 2010 Wiley-Liss, Inc.

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