title: Targeting the serrated pathway of colorectal cancer with mutation in BRAF.
abstract: A recently acknowledged morphological pathway to colorectal cancer originates from precursor polyps with a serrated appearance due to branching and folding of the colon epithelium. This serrated origin accounts for up to 30% of all colorectal tumors but these are heterogeneous regarding molecular characteristics and patient outcome. Here we review the current knowledge about the classification of this tumor subtype and its association with five key features: mutation status of the BRAF or KRAS genes, the CpG island methylation phenotype, microsatellite instability, immune cell infiltration, and overexpression of GTPase RAC1b. Subsequently, available therapeutic approaches for targeting these molecular characteristics are presented and critically discussed.
authors.affiliation: Department of Chemistry and Biochemistry, Faculty of Sciences, University of Lisbon, Portugal; BioISI - Biosystems & Integrative Sciences Institute, Faculty of Sciences, University of Lisbon, Portugal; Department of Human Genetics, National Health Institute 'Dr. Ricardo Jorge', Lisbon, Portugal.
authors.forename: Paulo
authors.initials: P
authors.lastname: Matos
authors.affiliation: BioISI - Biosystems & Integrative Sciences Institute, Faculty of Sciences, University of Lisbon, Portugal; Department of Human Genetics, National Health Institute 'Dr. Ricardo Jorge', Lisbon, Portugal.
authors.forename: Vânia
authors.initials: V
authors.lastname: Gonçalves
authors.affiliation: BioISI - Biosystems & Integrative Sciences Institute, Faculty of Sciences, University of Lisbon, Portugal; Department of Human Genetics, National Health Institute 'Dr. Ricardo Jorge', Lisbon, Portugal. Electronic address: peter.jordan@insa.min-saude.pt.
authors.forename: Peter
authors.initials: P
authors.lastname: Jordan
mesh_terms: D003106:Colon / Q000378:metabolism / Q000473:pathology; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000473:pathology; D018899:CpG Islands / Q000235:genetics; D019175:DNA Methylation / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D053842:Microsatellite Instability; D009154:Mutation; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics*; D015398:Signal Transduction; D020830:rac1 GTP-Binding Protein / Q000096:biosynthesis / Q000235:genetics*
chemical_list: C117307:KRAS protein, human; C107953:RAC1 protein, human; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; D016283:Proto-Oncogene Proteins p21(ras); D020830:rac1 GTP-Binding Protein
keywords: BRAF; Colorectal cancer; RAC1b; Serrated pathway; Therapeutic target; Tumor growth