Therapeutic relevance of molecular markers in colorectal cancer

Background Colorectal cancer (CRC) is a very common disease and one of the best characterized malignancies on the molecular level. Treatment options should be considered as a multimodal approach: curative surgery in early stages or metastasectomy in oligometastatic advanced stages, chemoradiotherapy and surgery for localized rectal cancer, and cytotoxic as well as targeted systemic therapy approaches in advanced disease. Methods Based on a selective literature search and analysis of the results, the use of molecular markers to predict treatment responses and prognosis is described. Results Determination of microsatellite instability (MSI-H) in early stage cancer is a clinically established procedure that is also found in guidelines. In addition to circulating tumor DNA, the immunoscore, the consensus molecular subtypes (CMS) classification, and genetic alterations in phosphoinositide-3 kinase (PI3K) and CDX2 could serve as additional factors. In metastatic colorectal cancer, RAS and BRAF status and the location of the primary tumor are decisive for therapy and should be determined before initiation of first-line therapy. New therapy approaches used as monotherapy or in combination enable targeted interventions at the immunological level, e.g., by means of checkpoint inhibition (CI), or targeted therapy in case of human epidermal growth factor receptor 2 (HER-2) amplification or neurotrophic tyrosine receptor kinase (NTRK) fusions. Conclusion Precise diagnostic methods have increased the knowledge and understanding of colorectal cancer as a heterogeneous disease, but the impact on clinical decisions still requires further assessment. In patients with hereditary cancer syndromes, the focus should be on the early detection of disease and should also take into account the consequences for the patients and their families.