Defining actionable mutations for oncology therapeutic development

被引：82

作者：

Carr, T. Hedley ^{[1
]}

McEwen, Robert ^{[1
]}

Dougherty, Brian ^{[3
]}

Johnson, Justin H. ^{[3
]}

Dry, Jonathan R. ^{[3
]}

Lai, Zhongwu ^{[3
]}

Ghazoui, Zara ^{[2
]}

Laing, Naomi M. ^{[3
]}

Hodgson, Darren R. ^{[2
]}

Cruzalegui, Francisco ^{[2
]}

Hollingsworth, Simon J. ^{[1
]}

Barrett, J. Carl ^{[3
]}

机构：

[1] AstraZeneca, Oncol IMED, Darwin Bldg,Cambridge Sci Pk, Cambridge CB4 0WG, England

[2] AstraZeneca, Oncol IMED, Macclesfield SK10 4TG, Cheshire, England

[3] AstraZeneca, Oncol IMED, Waltham, MA 02451 USA

来源：

NATURE REVIEWS CANCER | 2016年 / 16卷 / 05期

关键词：

SOMATIC MUTATIONS; DRUG DEVELOPMENT; CANCER GENOMICS; RESISTANCE; VALIDATION; INHIBITION; VARIANTS; TRIALS; RECOMMENDATIONS; CLASSIFICATION;

D O I：

10.1038/nrc.2016.35

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Genomic profiling of tumours in patients in clinical trials enables rapid testing of multiple hypotheses to confirm which genomic events determine likely responder groups for targeted agents. A key challenge of this new capability is defining which specific genomic events should be classified as 'actionable' (that is, potentially responsive to a targeted therapy), especially when looking for early indications of patient subgroups likely to be responsive to new drugs. This Opinion article discusses some of the different approaches being taken in early clinical development to define actionable mutations, and describes our strategy to address this challenge in early-stage exploratory clinical trials.

引用

页码：319 / 329

页数：11

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