title: Molecular Biomarkers in the Personalized Treatment of Colorectal Cancer.
abstract: Colorectal cancer (CRC) is a disease in which pathogenesis is influenced by genetic and epigenetic events that occur with tumor initiation and progression. Large variation exists in individual patient prognosis and response to chemotherapy, caused by molecular heterogeneity. Certain biomarkers have been identified that can predict clinical outcome beyond tumor staging, and inform treatment selection. Molecular testing is routinely performed in clinical practice for the selection of patients for targeted biological agents or immunotherapy, and is advocated for prognostic stratification. Estimating prognosis can avoid undertreatment or overtreatment and also guide the intensity of patient follow-up. Classifiers of CRC have been developed that integrate genetic and/or epigenetic features. The mutational status of KRAS and BRAF(V600E) oncogenes combined with analysis of the DNA mismatch repair system with/without the CpG island methylator phenotype (CIMP) has been shown to identify colon cancer subtypes with distinct clinical features and prognoses. Gene expression profiling has also been used to subtype CRCs and can overcome the limitations of single/limited gene testing. A recent effort identified 4 consensus molecular subtypes of biological relevance that were associated with different patient outcomes. Efforts to validate and refine these subtypes to include additional genomic features are ongoing. The focus of this article is to highlight molecular markers that can inform clinical decision-making in patients with CRC.
authors.affiliation: Division of Gastroenterology and Hepatology, Mayo Clinic and Mayo Cancer Center, Rochester, Minnesota; Division of Medical Oncology, Mayo Clinic and Mayo Cancer Center, Rochester, Minnesota. Electronic address: sinicrope.frank@mayo.edu.
authors.forename: Frank A
authors.initials: FA
authors.lastname: Sinicrope
authors.affiliation: Division of Gastroenterology and Hepatology, Mayo Clinic and Mayo Cancer Center, Rochester, Minnesota.
authors.forename: Koichi
authors.initials: K
authors.lastname: Okamoto
authors.affiliation: Division of Medical Oncology, Mayo Clinic and Mayo Cancer Center, Rochester, Minnesota.
authors.forename: Pashtoon M
authors.initials: PM
authors.lastname: Kasi
authors.affiliation: Division of Gastroenterology and Hepatology, Mayo Clinic and Mayo Cancer Center, Rochester, Minnesota.
authors.forename: Hisato
authors.initials: H
authors.lastname: Kawakami
mesh_terms: D015179:Colorectal Neoplasms / Q000145:classification / Q000175:diagnosis* / Q000473:pathology / Q000628:therapy*; D045643:DNA Repair Enzymes / Q000235:genetics; D004358:Drug Therapy / Q000379:methods; D020869:Gene Expression Profiling; D005819:Genetic Markers; D006801:Humans; D007167:Immunotherapy / Q000379:methods; D057285:Precision Medicine / Q000379:methods*; D011379:Prognosis; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics
chemical_list: D005819:Genetic Markers; C117307:KRAS protein, human; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; D016283:Proto-Oncogene Proteins p21(ras); D045643:DNA Repair Enzymes
keywords: Anti-EGFR; Anti-VEGF; BRAF; Biologics; Colorectal Cancer; DNA Mismatch Repair; Immunotherapy; MSI; Molecular Subtypes; Predictive Markers; Prognostic Markers; RAS; Targeted Therapy