Bioethics Blogs

Acting on “Actionable Mutations”

The new buzzword in personalized cancer medicine is “actionable mutation”. This label is given to the genetic aberrations that are present in some patients’ tumors, and that are intended targets of new drugs. Increasingly, treatment decisions in routine clinical care, and enrollment in trials are being guided by the concept of “actionable mutations”.

However, determining “actionablility” is an ongoing challenge. The function of a particular mutation, to what degree it is responsible for driving a given malignancy, and how easily it can be targeted by a specific therapy, all affect how “actionable” it is. Further, a tumor’s genomic profiling can vary depending on which tissues are biopsied (ie primary and metastatic tumor sites), or when they are biopsied (before and after particular treatment regiments). “Actionability” of mutations may not be a stable variable that is easily transferred from one clinical setting to another. Instead, the concept of actionability invites further clarification on where a when and these genes should be screened.

Unfortunately, lack of clarity on the definition of “actionable mutations” has not prevented its uptake in either the commercial or scientific medical communities. For example, upon physician request, diagnostics company Foundation One will sequence over 300 genes that are known or likely targets of a specific therapy and provide clinicians with a report listing all of their patient’s actionable mutations. These are mutations they define as all those that can be targeted by both therapies currently approved for their indication as well as those approved for other malignancies (off-label). Further, some mutations are designated “Equivocal” signifying that there is some, but not confirmed evidence, supporting an aberration in a patient’s sample, or “Subclonal” where an abnormality only exists in less than 10% of a patient’s tumor.

The views, opinions and positions expressed by these authors and blogs are theirs and do not necessarily represent that of the Bioethics Research Library and Kennedy Institute of Ethics or Georgetown University.