Evidence-Based Precision Oncology with the Cancer Targetome

A core tenet of precision oncology is the rational choice of drugs to interact with patient-specific biological targets of interest, but it is currently difficult for researchers to obtain consistent and well-supported target information for pharmaceutical drugs. We review current drug–target interaction resources and critically assess how supporting evidence is handled. We introduce the concept of a unified Cancer Targetome to aggregate drug–target interactions in an evidence-based framework. We discuss current unmet needs and the implications for evidence-based clinical omics. The focus of this review is precision oncology but the discussion is highly relevant to targeted therapies in any area. Precision oncology, which aims to rationally select treatments for patients based on their genetic information, has a key dependency on drug-to-target annotation that is often overlooked. While ‘patient-specific’ treatment broadly encompasses all aspects of a patient's health, such as additional diagnoses, other prescribed medications, or even adverse effects experienced in response to therapy, our scope for this Review is focused narrowly on use of the term ‘patient specific’ to mean those biological targets specific to a patient's cancerous cells that may be modulated to have a therapeutic effect. Drug–target annotation is often heavily biased towards primary targets, with limited or difficult-to-find information on secondary targets. Resources for drug–target interactions differ in coverage, consistency, and evidence curation, which makes it challenging for researchers to obtain credible and reproducible drug-to-target annotation.