title: Combined KRAS and TP53 mutation status is not predictive in CAPOX-treated metastatic colorectal cancer.
abstract: BACKGROUND
  The response of colorectal tumours to chemotherapy is highly variable. Preclinical work has shown that the Kirsten ras (KRAS) oncogene sensitizes colorectal tumour cells to oxaliplatin and capecitabine in a wild-type tumour suppressor p53 (TP53)-dependent manner. Therefore, whether or not the combined mutation status of KRAS and TP53 could predict response to chemotherapy in metastatic colorectal cancer was tested.
  
  
  METHODS
  A subgroup of patients from the CAIRO2 study (randomized phase III study on capecitabine, oxaliplatin, bevacizumab with or without cetuximab in first-line advanced colorectal cancer) that received capecitabine plus oxaliplatin (CAPOX) treatment in combination with bevacizumab was selected. The tumours were analyzed for KRAS and TP53 mutations by PCR/sequencing. The relationship between tumour response and genotype was analyzed.
  
  
  RESULTS
  The following KRAS/TP53 genotypes were identified: KRASmut/TP53mut n=21, KRASmut/TP53wt n=20, KRASwt/TP53mut n=25, KRASwt/TP53wt n=15. No genotype was associated with a significantly better or worse progression-free or overall survival.
  
  
  CONCLUSIONS
  The combined mutation status of KRAS and TP53 does not predict response to CAPOX in patients with metastasized colorectal cancer.
authors.affiliation: Department of Surgery, University Medical Center Utrecht, Heidelberglaan 100, 3584CX Utrecht, the Netherlands.
authors.forename: Menno T
authors.initials: MT
authors.lastname: De Bruijn
authors.forename: Daniëlle A E
authors.initials: DA
authors.lastname: Raats
authors.forename: Jolien
authors.initials: J
authors.lastname: Tol
authors.forename: John
authors.initials: J
authors.lastname: Hinrichs
authors.forename: Steven
authors.initials: S
authors.lastname: Teerenstra
authors.forename: Cornelis J A
authors.initials: CJ
authors.lastname: Punt
authors.forename: Inne H M Borel
authors.initials: IH
authors.lastname: Rinkes
authors.forename: Onno
authors.initials: O
authors.lastname: Kranenburg
mesh_terms: D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D061067:Antibodies, Monoclonal, Humanized; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D000068258:Bevacizumab; D000069287:Capecitabine; D000068818:Cetuximab; D017326:Clinical Trials, Phase III as Topic; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000556:secondary*; D004273:DNA, Neoplasm / Q000235:genetics; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D005472:Fluorouracil / Q000008:administration & dosage / Q000031:analogs & derivatives; D006801:Humans; D009154:Mutation / Q000235:genetics*; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D000077150:Oxaliplatin; D016133:Polymerase Chain Reaction; D011379:Prognosis; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D016283:Proto-Oncogene Proteins p21(ras); D015996:Survival Rate; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*; D018631:ras Proteins / Q000235:genetics*
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D004273:DNA, Neoplasm; C117307:KRAS protein, human; D009944:Organoplatinum Compounds; D011518:Proto-Oncogene Proteins; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D000077150:Oxaliplatin; D003841:Deoxycytidine; D000068258:Bevacizumab; D000069287:Capecitabine; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins; D000068818:Cetuximab; D005472:Fluorouracil