Clonal Heterogeneity and Tumor Evolution: Past, Present, and the Future

被引：1824

作者：

McGranahan, Nicholas ^{[1
,2
]}

Swanton, Charles ^{[1
,2
,3
]}

机构：

[1] UCL, Inst Canc, Canc Res UK Lung Canc Ctr Excellence, Paul OGorman Bldg,72 Huntley St, London WC1E 6BT, England

[2] Francis Crick Inst, Translat Canc Therapeut Lab, 1 Midland Rd, London NW1 1AT, England

[3] Univ Coll London Hosp, Dept Med Oncol, 235 Euston Rd, London NW1 2BU, England

来源：

CELL | 2017年 / 168卷 / 04期

基金：

欧洲研究理事会; 英国惠康基金; 英国医学研究理事会;

关键词：

PAIRED EXOME ANALYSIS; WHOLE-GENOME; MUTATIONAL PROCESSES; CANCER EVOLUTION; COPY NUMBER; INTRATUMOR HETEROGENEITY; COLLATERAL SENSITIVITY; ACQUIRED-RESISTANCE; ESOPHAGEAL ADENOCARCINOMA; CHROMOSOMAL INSTABILITY;

D O I：

10.1016/j.cell.2017.01.018

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Intratumor heterogeneity, which fosters tumor evolution, is a key challenge in cancer medicine. Here, we review data and technologies that have revealed intra-tumor heterogeneity across cancer types and the dynamics, constraints, and contingencies inherent to tumor evolution. We emphasize the importance of macro-evolutionary leaps, often involving large-scale chromosomal alterations, in driving tumor evolution and metastasis and consider the role of the tumor microenvironment in engendering heterogeneity and drug resistance. We suggest that bold approaches to drug development, harnessing the adaptive properties of the immune-microenvironment while limiting those of the tumor, combined with advances in clinical trial-design, will improve patient outcome.

引用

页码：613 / 628

页数：16

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