title: KRAS exon 2 mutations influence activity of regorafenib in an SW48-based disease model of colorectal cancer.
abstract: OBJECTIVE
  To investigate the impact of KRAS mutation variants on the activity of regorafenib in SW48 colorectal cancer cells.
  
  
  METHODS
  Activity of regorafenib was evaluated in isogenic SW48 KRAS wild-type (WT) and mutant cells. Subcutaneous xenografts (KRAS WT and G12C mutant variants) in NOD/SCID mice were analyzed to elucidate the effect of regorafenib treatment in vivo.
  
  
  RESULTS
  Compared with KRAS WT cells, all mutant variants seemed associated with some degree of resistance to regorafenib-treatment in vitro. In vivo, activation of apoptosis (TUNEL) and reduction of proliferation (Ki67) after treatment with regorafenib were more pronounced in KRAS WT tumors as compared with G12C variants.
  
  
  CONCLUSIONS
  In SW48 cells, exon 2 mutations of the KRAS gene may influence antitumor effects of regorafenib.
authors.affiliation: Department of Surgery, University Hospital Grosshadern, University of Munich, Munich, Germany.|German Cancer Consortium (DKTK), Heidelberg, Germany.|Division of Experimental Surgery, Department of Surgery, Otto-von-Guericke-University, Magdeburg, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Camaj
authors.affiliation: Department of Surgery, University Hospital Grosshadern, University of Munich, Munich, Germany.
authors.forename: Stefano
authors.initials: S
authors.lastname: Primo
authors.affiliation: Department of Surgery, University Hospital Grosshadern, University of Munich, Munich, Germany.|Division of Experimental Surgery, Department of Surgery, Otto-von-Guericke-University, Magdeburg, Germany.
authors.forename: Yan
authors.initials: Y
authors.lastname: Wang
authors.affiliation: German Cancer Consortium (DKTK), Heidelberg, Germany.|Department of Medicine III, University Hospital Grosshadern, University of Munich, Munich, Germany.
authors.forename: Volker
authors.initials: V
authors.lastname: Heinemann
authors.affiliation: Department of Surgery, University Hospital Grosshadern, University of Munich, Munich, Germany.|Division of Experimental Surgery, Department of Surgery, Otto-von-Guericke-University, Magdeburg, Germany.
authors.forename: Yue
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: German Cancer Consortium (DKTK), Heidelberg, Germany.|Institute of Medical Informatics, Biometry & Epidemiology, University of Munich, Munich, Germany.
authors.forename: Ruediger Paul
authors.initials: RP
authors.lastname: Laubender
authors.affiliation: German Cancer Consortium (DKTK), Heidelberg, Germany.|Department of Medicine III, University Hospital Grosshadern, University of Munich, Munich, Germany.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Stintzing
authors.affiliation: German Cancer Consortium (DKTK), Heidelberg, Germany.|Department of Medicine III, University Hospital Grosshadern, University of Munich, Munich, Germany.
authors.forename: Clemens
authors.initials: C
authors.lastname: Giessen-Jung
authors.affiliation: German Cancer Consortium (DKTK), Heidelberg, Germany.|Institute of Pathology, University of Munich, Munich, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Jung
authors.affiliation: Department of Surgery, University Hospital Grosshadern, University of Munich, Munich, Germany.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Gamba
authors.affiliation: Department of Surgery, University Hospital Grosshadern, University of Munich, Munich, Germany.|German Cancer Consortium (DKTK), Heidelberg, Germany.|Division of Experimental Surgery, Department of Surgery, Otto-von-Guericke-University, Magdeburg, Germany.
authors.forename: Christiane Josephine
authors.initials: CJ
authors.lastname: Bruns
authors.affiliation: German Cancer Consortium (DKTK), Heidelberg, Germany.|Department of Medicine III, University Hospital Grosshadern, University of Munich, Munich, Germany.
authors.forename: Dominik Paul
authors.initials: DP
authors.lastname: Modest
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D015179:Colorectal Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D005091:Exons; D006801:Humans; D051379:Mice; D009154:Mutation; D010671:Phenylurea Compounds / Q000008:administration & dosage*; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics*; D011725:Pyridines / Q000008:administration & dosage*; D023041:Xenograft Model Antitumor Assays
chemical_list: C117307:KRAS protein, human; D010671:Phenylurea Compounds; D011725:Pyridines; C559147:regorafenib; D016283:Proto-Oncogene Proteins p21(ras)
keywords: ELK; KRAS; MAPK pathway; colorectal cancer; regorafenib