Targeting chromosomal instability and tumour heterogeneity in HER2-positive breast cancer.
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.
Burrell
Rebecca A
RA
Translational Cancer Therapeutics Laboratory, London Research Institute, 44 Lincoln's Inn Fields, London WC2A 3PX, UK.
Juul
Nicolai
N
Johnston
Stephen R
SR
Reis-Filho
Jorge S
JS
Szallasi
Zoltan
Z
Swanton
Charles
C
D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D002453:Cell Cycle / Q000187:drug effects; D043171:Chromosomal Instability / Q000187:drug effects / Q000235:genetics*; D005260:Female; D018740:Genetic Heterogeneity / Q000187:drug effects; D006801:Humans; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*
D000970:Antineoplastic Agents; D018719:Erb-b2 Receptor Tyrosine Kinases