Opinion | Published:

Defining actionable mutations for oncology therapeutic development

Nature Reviews Cancer volume 16, pages 319329 (2016) | Download Citation

Abstract

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.

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Author information

Author notes

    • T. Hedley Carr
    •  & Robert McEwen

    T.H.C. and R.M. contributed equally to this work.

Affiliations

  1. Oncology IMED, AstraZeneca, Darwin Building, Cambridge Science Park, Cambridge CB4 0WG, UK.

    • T. Hedley Carr
    • , Robert McEwen
    •  & Simon J. Hollingsworth
  2. Oncology IMED, AstraZeneca, Alderley Park, Macclesfield SK10 4TG, UK.

    • Zara Ghazoui
    • , Darren R. Hodgson
    •  & Francisco Cruzalegui
  3. Oncology IMED, AstraZeneca, Waltham, Massachusetts 02451, USA.

    • Brian Dougherty
    • , Justin H. Johnson
    • , Jonathan R. Dry
    • , Zhongwu Lai
    • , Naomi M. Laing
    •  & J. Carl Barrett

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Competing interests

The authors are employees of AstraZeneca and hold shares in the company.

Corresponding authors

Correspondence to T. Hedley Carr or Robert McEwen.

About this article

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DOI

https://doi.org/10.1038/nrc.2016.35

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