Biomarker-guided therapy for colorectal cancer: strength in complexity

The number of molecularly stratified treatment options available to patients with colorectal cancer (CRC) is increasing, with a parallel rise in the use of biomarkers to guide prognostication and treatment decision-making. The increase in both the number of biomarkers and their use has resulted in a progressively complex situation, evident both from the extensive interactions between biomarkers and from their sometimes complex associations with patient prognosis and treatment benefit. Current and emerging biomarkers also reflect the genomic complexity of CRC, and include a wide range of aberrations such as point mutations, amplifications, fusions and hypermutator phenotypes, in addition to global gene expression subtypes. In this Review, we provide an overview of current and emerging clinically relevant biomarkers and their role in the management of patients with CRC, illustrating the intricacies of biomarker interactions and the growing treatment opportunities created by the availability of comprehensive molecular profiling.