title: Targeting RAS signaling pathway as a potential therapeutic target in the treatment of colorectal cancer.
abstract: The V-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS) is frequently dysregulated in colorectal cancer (CRC). It is involved in the modulation of several downstream effectors, that include: Raf/Mek/Erk, PI3K/Akt, RalGDS/p38MAPK, and Rac/Rho, and thereby influences tumorigenesis, the invasive behaviors of tumor cell, and resistance to therapy. There is growing evidence exploring the use of drugs that target these pathways in the treatment of CRC. Cetuximab has been approved for CRC patients without a KRAS mutation, or for EGFR-expressing metastatic CRC, although some of the patients have a mutation of KRAS and NRAS. This review summarizes the recent knowledge about the therapeutic potential of targeting RAS with particular emphasis on recent preclinical and clinical studies in treatment of CRC.
authors.affiliation: Department of Modern Sciences and Technologies, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
authors.forename: Afsane
authors.initials: A
authors.lastname: Bahrami
authors.affiliation: Metabolic Syndrome Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.|Department of Medical Biochemistry, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
authors.forename: Seyed Mahdi
authors.identifier: http://orcid.org/0000-0002-5247-4043
authors.initials: SM
authors.lastname: Hassanian
authors.affiliation: Cancer Research Center, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
authors.forename: Soodabeh
authors.initials: S
authors.lastname: ShahidSales
authors.affiliation: Department of Modern Sciences and Technologies, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
authors.forename: Zahra
authors.initials: Z
authors.lastname: Farjami
authors.affiliation: Department of Gynecology Oncology, Woman Health Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.
authors.forename: Malihe
authors.initials: M
authors.lastname: Hasanzadeh
authors.affiliation: Cancer Research Center, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
authors.forename: Kazem
authors.initials: K
authors.lastname: Anvari
authors.affiliation: Cancer Research Center, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
authors.forename: Amir
authors.initials: A
authors.lastname: Aledavood
authors.affiliation: Metabolic Syndrome Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.
authors.forename: Mina
authors.initials: M
authors.lastname: Maftouh
authors.affiliation: Brighton & Sussex Medical School, Division of Medical Education, Falmer, Brighton, Sussex, UK.
authors.forename: Gordon A
authors.initials: GA
authors.lastname: Ferns
authors.affiliation: Department of Physiology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
authors.forename: Majid
authors.identifier: http://orcid.org/0000-0002-4968-0962
authors.initials: M
authors.lastname: Khazaei
authors.affiliation: Metabolic Syndrome Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.|Cancer Research Center, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
authors.forename: Amir
authors.initials: A
authors.lastname: Avan
mesh_terms: D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D000074322:Antineoplastic Agents, Immunological / Q000627:therapeutic use*; D002471:Cell Transformation, Neoplastic; D000068818:Cetuximab / Q000627:therapeutic use*; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000235:genetics; D020558:GTP Phosphohydrolases / Q000037:antagonists & inhibitors / Q000235:genetics; D006801:Humans; D008565:Membrane Proteins / Q000037:antagonists & inhibitors / Q000235:genetics; D000077544:Panitumumab; D010671:Phenylurea Compounds / Q000627:therapeutic use; D016283:Proto-Oncogene Proteins p21(ras) / Q000037:antagonists & inhibitors* / Q000235:genetics* / Q000378:metabolism; D011725:Pyridines / Q000627:therapeutic use
chemical_list: D000911:Antibodies, Monoclonal; D000074322:Antineoplastic Agents, Immunological; C117307:KRAS protein, human; D008565:Membrane Proteins; D010671:Phenylurea Compounds; D011725:Pyridines; C559147:regorafenib; D000077544:Panitumumab; C512478:EGFR protein, human; D066246:ErbB Receptors; D020558:GTP Phosphohydrolases; C579846:NRAS protein, human; D016283:Proto-Oncogene Proteins p21(ras); D000068818:Cetuximab
keywords: KRAS; cetuximab; colorectal cancer; novel anticancer agent