Targeting Chromosomal Instability and Tumour Heterogeneity in HER2-Positive Breast Cancer

Rebecca A. Burrell, Nicolai Juul Birkbak, Stephen R. Johnston, Jorge S. Reis-Filho, Zoltan Imre Szallasi, Charles Swanton

    Research output: Contribution to journalJournal articleResearchpeer-review

    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.
    Original languageEnglish
    JournalJournal of Cellular Biochemistry
    Volume111
    Issue number4
    Pages (from-to)782-790
    ISSN0730-2312
    DOIs
    Publication statusPublished - 2010

    Keywords

    • HER2
    • CHROMOSOMAL INSTABILITY
    • CEP17
    • BREAST CANCER
    • DRUG RESISTANCE
    • MICROTUBULE
    • TUMOUR HETEROGENEITY

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