Towards the era of precision medicine in metastatic colorectal cancer

Colorectal cancer (CRC) represents a heterogeneous group of dynamic biological phenomena with differing sets of genetic events, accompanying immune responses and influences of exogenous factors, providing a challenge for personalised therapeutic approaches.1 These personalised treatments most often involve kinase inhibitors or monoclonal antibodies that target specific alterations known to drive the proliferation and survival of cancer cells.2 In this scenario, the epidermal growth factor receptor (EGFR) family plays a key role in tumour growth and progression, but its use is limited by the presence of pre-existing innate resistance mechanisms or by the ability of cancer cells to acquire resistance to therapy.2 3 RAS mutation status is the only negative predictive biomarker in the management of CRC. Additional molecular features associated with resistance to anti-EGFR therapy in many preclinical studies, including PIK3CA mutation, phosphatase and tensin homologue loss, BRAF mutation, human epidermal growth factor receptor 2 (HER2) and secondary EGFR mutations, have been studied, but no one has been incorporated routinely in clinical practice.2 3 Intriguingly, …