Features: Volume 111, Number 4

• Book ID: 102304618
• Publisher: John Wiley and Sons
• Year: 2010
• Tongue: English
• Weight: 130 KB
• Volume: 111
• Category: Article
• ISSN: 0730-2312
• DOI: 10.1002/jcb.22939

✦ Synopsis

Intrinsic and acquired drug resistance represent a major obstacle to the successful treatment of cancer. Tumour heterogeneity and chromosomal instability (CIN) are likely to be important determinants of drug sensitivity, for example, CIN is associated with taxane resistance but exhibits relative sensitivity to platinum based therapies in ovarian cancer. A meta-analysis of patients with HER2 positive breast cancer suggests there is considerable heterogeneity in tumour CIN status between patients. Burrell et al propose a model examining the effect of the distribution of CIN in HER2+ breast cancer in determining the response profi les seen in clinical trials for this patient group. Evidence indicates that HER2 inhibitors may target CIN cells, consistent with evidence that HER2 signalling may be associated with chromosomal instability. Given the relationship between CIN and resistance to taxanes, together with data demonstrating that EGFR/HER2 blockade may reverse CIN in cancer cell models, a biological rationale is presented that may explain the additive benefi t witnessed in clinical trials with the combination of taxanes and HER2 receptor blockade in HER2+ breast cancer. This model suggests that the distribution of tumour CIN status should be considered when designing combinatorial therapeutic regimens and when interpreting clinical trial data.