title: Molecular pathways and cellular metabolism in colorectal cancer.
abstract: Colorectal cancer (CRC) is, for sporadic forms, most strongly related to lifestyle factors. The epidemic of obesity and physical inactivity has great impact on disease patterns. Likewise, an altered metabolism has consequences at the cellular and molecular level with implications for cancer initiation and growth. Understanding the genetic hallmarks of cancers has improved over the years and now also includes cancer metabolic reprogramming. The initiation of cancer through genetic instability, including chromosomal instability, microsatellite instability and epigenetic silencing through the CpG island methylator phenotype follows pathways with distinct clinical, pathological, and genetic characteristics. These can potentially be used for molecular classification and comprehensive tumor profiling for improved diagnostics, prognosis and treatment in CRC. For one, epidermal growth factor receptor-directed treatment now considerably prolongs survival in metastatic disease, but defining the true responders from non-responders has emerged as complex. Further, the use of both non-steroidal anti-inflammatory drugs including cyclooxygenase-2 inhibitors is associated with a decreased incidence of adenoma and reduced mortality rate of CRC. This review gives a brief yet updated overview of the current understanding of CRC as a genetic and molecular disease with potential for clinical pathways of prevention, improved prediction and better prognosis in the future.
authors.affiliation: Department of Gastrointestinal Surgery, Stavanger University Hospital, Stavanger, Norway.
authors.forename: Hanne R
authors.initials: HR
authors.lastname: Hagland
authors.forename: Marianne
authors.initials: M
authors.lastname: Berg
authors.forename: Ingunn W
authors.initials: IW
authors.lastname: Jolma
authors.forename: Arne
authors.initials: A
authors.lastname: Carlsen
authors.forename: Kjetil
authors.initials: K
authors.lastname: Søreide
mesh_terms: D000236:Adenoma / Q000235:genetics / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D063646:Carcinogenesis / Q000235:genetics / Q000378:metabolism; D043171:Chromosomal Instability / Q000235:genetics; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000378:metabolism*; D018899:CpG Islands / Q000235:genetics; D019175:DNA Methylation; D057890:Epigenomics; D005838:Genotype; D006801:Humans; D009154:Mutation; D010641:Phenotype; D011379:Prognosis
chemical_list: D014408:Biomarkers, Tumor