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The Journal of Clinical Investigation (JCI)Targeting Mutations in Cancer

Targeted therapy gene mutations may: (a) encode a protein that can be targeted in a manner distinct from the WT protein; (b) cause abnormal activation of a protein that is druggable but for which mutant-specific targeting has not been achieved; or (c) create novel molecular dependencies that are druggable. This article describe key examples of genetic drivers and associated modes of druggability, considers the clinical and research challenges in the field, and discusses new approaches to maximizing therapeutic benefit of targeted therapies.