How Darwinian models inform therapeutic failure initiated by clonal heterogeneity in cancer medicine

被引：313

作者：

Gerlinger, M. ^{[1
,2
]}

Swanton, C. ^{[1
,3
,4
]}

机构：

[1] Canc Res UK London Res Inst, Translat Canc Therapeut Lab, London WC2A 3LY, England

[2] Barts & London Queen Marys Sch Med & Dent, Dept Med Oncol, Inst Canc, London, England

[3] Royal Marsden Hosp, Dept Med, Breast Unit, Sutton SM2 5PT, Surrey, England

[4] Royal Marsden Hosp, Dept Med, Drug Dev Unit, Sutton SM2 5PT, Surrey, England

来源：

BRITISH JOURNAL OF CANCER | 2010年 / 103卷 / 08期

基金：

英国医学研究理事会;

关键词：

drug resistance; evolution; genomic instability; heterogeneity; CELL LUNG-CANCER; CHRONIC MYELOID-LEUKEMIA; LYMPHOBLASTIC-LEUKEMIA; MULTIDRUG-RESISTANCE; MSH6; MUTATIONS; GENE MUTATION; ABL GENE; DRUG; EVOLUTIONARY; CHEMOTHERAPY;

D O I：

10.1038/sj.bjc.6605912

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Carcinogenesis is an evolutionary process that establishes the 'hallmarks of cancer' by natural selection of cell clones that have acquired advantageous heritable characteristics. Evolutionary adaptation has also been proposed as a mechanism that promotes drug resistance during systemic cancer therapy. This review summarises the evidence for the evolution of resistance to cytotoxic and targeted anti-cancer drugs according to Darwinian models and highlights the roles of genomic instability and high intra-tumour genetic heterogeneity as major accelerators of this evolutionary process. Clinical implications and strategies that may prevent the evolution of resistance or target the origins of genetic heterogeneity are discussed. New technologies to measure intra-tumour heterogeneity and translational research on serial biopsies of cancer lesions during and after therapeutic intervention are identified as key areas to further the understanding of determinants and mechanisms of the evolution of drug resistance. British Journal of Cancer (2010) 103, 1139-1143. doi:10.1038/sj.bjc.6605912 www.bjcancer.com Published online 28 September 2010 (C) 2010 Cancer Research UK

引用

页码：1139 / 1143

页数：5

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