title: Genomic diversity of colorectal cancer: Changing landscape and emerging targets.
abstract: Improvements in screening and preventive measures have led to an increased detection of early stage colorectal cancers (CRC) where patients undergo treatment with a curative intent. Despite these efforts, a high proportion of patients are diagnosed with advanced stage disease that is associated with poor outcomes, as CRC remains one of the leading causes of cancer-related deaths in the world. The development of next generation sequencing and collaborative multi-institutional efforts to characterize the cancer genome has afforded us with a comprehensive assessment of the genomic makeup present in CRC. This knowledge has translated into understanding the prognostic role of various tumor somatic variants in this disease. Additionally, the awareness of the genomic alterations present in CRC has resulted in an improvement in patient outcomes, largely due to better selection of personalized therapies based on an individual's tumor genomic makeup. The benefit of various treatments is often limited, where recent studies assessing the genomic diversity in CRC have identified the development of secondary tumor somatic variants that likely contribute to acquired treatment resistance. These studies have begun to alter the landscape of treatment for CRC that include investigating novel targeted therapies, assessing the role of immunotherapy and prospective, dynamic assessment of changes in tumor genomic alterations that occur during the treatment of CRC.
authors.affiliation: Daniel H Ahn, Tanios Bekaii-Saab, Division of Medical Oncology, Mayo Clinic, Phoenix, AZ 85054, United States.
authors.forename: Daniel H
authors.initials: DH
authors.lastname: Ahn
authors.affiliation: Daniel H Ahn, Tanios Bekaii-Saab, Division of Medical Oncology, Mayo Clinic, Phoenix, AZ 85054, United States.
authors.forename: Kristen K
authors.initials: KK
authors.lastname: Ciombor
authors.affiliation: Daniel H Ahn, Tanios Bekaii-Saab, Division of Medical Oncology, Mayo Clinic, Phoenix, AZ 85054, United States.
authors.forename: Sameh
authors.initials: S
authors.lastname: Mikhail
authors.affiliation: Daniel H Ahn, Tanios Bekaii-Saab, Division of Medical Oncology, Mayo Clinic, Phoenix, AZ 85054, United States.
authors.forename: Tanios
authors.initials: T
authors.lastname: Bekaii-Saab
mesh_terms: D015179:Colorectal Neoplasms / Q000235:genetics* / Q000628:therapy; D053843:DNA Mismatch Repair / Q000235:genetics; D004273:DNA, Neoplasm / Q000235:genetics*; D023281:Genomics; D006801:Humans; D058990:Molecular Targeted Therapy; D009154:Mutation; D057285:Precision Medicine; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics; D019859:Proto-Oncogene Proteins c-met / Q000235:genetics; D051096:Proto-Oncogene Proteins c-ret / Q000235:genetics; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics; D017468:Receptors, Fibroblast Growth Factor / Q000235:genetics
chemical_list: D004273:DNA, Neoplasm; D048493:Proto-Oncogene Proteins B-raf; D019859:Proto-Oncogene Proteins c-met; D051096:Proto-Oncogene Proteins c-ret; D016283:Proto-Oncogene Proteins p21(ras); D018719:Erb-b2 Receptor Tyrosine Kinases; D017468:Receptors, Fibroblast Growth Factor; C117307:KRAS protein, human; C508053:ERBB2 protein, human; C099282:RET protein, human; C482119:BRAF protein, human
keywords: BRAF mutation; Colorectal cancer; Genomic diversity; KRAS mutation; Tumor DNA