Drugs are designed to bind to specific protein targets. Common genetic variation affects the drug binding site and action of the protein and can affect the efficacy of a drug, but this is generally not considered in the preclinical testing prior to a clinical trial. For the most popular precision oncology therapeutics, some resistance mutations are later identified and considered when prescribing a companion diagnostic test. However, there is no systematic approach to identify drug resistance. If this information were available to oncologists, it could be used to select among different drugs for more effective data-driven treatment.