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Updated: Mar 22, 2026
Next Generation Sequencing for the Detection of Actionable Mutations in Solid and Liquid Tumors
Published on: September 20, 2016
Defining actionable mutations for oncology therapeutic development
T Hedley Carr1, Robert McEwen1, Brian Dougherty2
1Oncology IMED, AstraZeneca, Darwin Building, Cambridge Science Park, Cambridge CB4 0WG, UK.
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.
Insights
Genomic profiling in clinical trials helps identify patient subgroups likely to respond to targeted therapies. Defining actionable mutations is crucial for this process, especially in early drug development.
Area of Science:
- Oncology
- Genomics
- Clinical Trials
Background:
- Genomic profiling of tumors in clinical trials allows rapid hypothesis testing.
- Identifying genomic events that predict response to targeted agents is essential.
- Classifying genomic events as 'actionable' is a key challenge in early drug development.
Purpose of the Study:
- To discuss various approaches for defining actionable mutations in early clinical development.
- To present a specific strategy for addressing this challenge in early-stage exploratory trials.
Main Methods:
- Review of current strategies for defining actionable mutations.
- Description of a proposed strategy for early-stage exploratory clinical trials.
Main Results:
- The article outlines different methodologies for classifying actionable genomic alterations.
- It highlights the importance of a defined strategy for identifying patient subgroups.
Conclusions:
- Defining actionable mutations is critical for optimizing targeted therapy development.
- A clear strategy is needed to effectively utilize genomic profiling in early clinical trials to identify responsive patient populations.
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