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

✍ Scribed by Rebecca A. Burrell; Nicolai Juul; Stephen R. Johnston; Jorge S. Reis-Filho; Zoltan Szallasi; Charles Swanton

• Publisher: John Wiley and Sons
• Year: 2010
• Tongue: English
• Weight: 181 KB
• Volume: 111
• Category: Article
• ISSN: 0730-2312
• DOI: 10.1002/jcb.22781

✦ Synopsis

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.