title: KRAS G13D Mutation and Sensitivity to Cetuximab or Panitumumab in a Colorectal Cancer Cell Line Model.
abstract: BACKGROUND
  The treatment of metastatic colorectal cancer (mCRC) includes drugs targeting the epidermal growth factor receptor (EGFR). Mutation in codon 12 or 13 in the Kirsten rat sarcoma viral oncogene homolog (KRAS) gene, downstream of the EGFR, evokes constitutive activation of the RAS/RAF/MAPK signaling pathway and correlates with resistance to anti-EGFR monoclonal antibody (mAb) therapies. However, a retrospective study reported that a proportion of patients with the KRAS G13D mutation may respond to cetuximab. A similar analysis for panitumumab was not as conclusive. We sought to determine the sensitivity of CRC cell lines to cetuximab or panitumumab treatment and to investigate the correlation of the KRAS mutational status of the CRC cell lines to the responsiveness to cetuximab or panitumumab.
  
  
  METHODS
  To determine the responsiveness of CRC cell lines to cetuximab or panitumumab, cell lines were treated with an optimized concentration of each mAb, and proliferation assays were conducted.
  
  
  RESULTS
  After treatment with cetuximab or panitumumab, at the optimum concentration of 8 μg/well, the KRAS G13D mutant cell lines HCT-116, LoVo, and T84 showed intermediate sensitivity to both treatments, between the resistant KRAS G12V mutant cell line SW480 and the sensitive KRAS wild-type cell line LIM1215. One of the G13D cell lines was significantly more sensitive to panitumumab than to cetuximab (P = .02).
  
  
  CONCLUSIONS
  The specific KRAS mutation determines the responsiveness to anti-EGFR monoclonal antibody treatment, corresponding to reported clinical observations.
authors.affiliation: Haematology-Oncology Department Basil Hetzel Institute for Translational Health Research The Queen Elizabeth Hospital Woodville, South Australia, Australia ; Department of Physiology School of Medical Sciences University of Adelaide Adelaide, South Australia, Australia.
authors.forename: Shalini Sree
authors.initials: SS
authors.lastname: Kumar
authors.affiliation: Medical Oncology Unit The Queen Elizabeth Hospital Woodville, South Australia, Australia ; School of Medicine University of Adelaide Adelaide, South Australia, Australia.
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Price
authors.affiliation: School of Medicine Royal College of Surgeons in Ireland Bahrain Campus Bahrain.
authors.forename: Omar
authors.initials: O
authors.lastname: Mohyieldin
authors.affiliation: School of Medicine University of Adelaide Adelaide, South Australia, Australia.
authors.forename: Matthew
authors.initials: M
authors.lastname: Borg
authors.affiliation: Medical Oncology Unit The Queen Elizabeth Hospital Woodville, South Australia, Australia ; School of Medicine University of Adelaide Adelaide, South Australia, Australia.
authors.forename: Amanda
authors.initials: A
authors.lastname: Townsend
authors.affiliation: Haematology-Oncology Department Basil Hetzel Institute for Translational Health Research The Queen Elizabeth Hospital Woodville, South Australia, Australia ; Department of Physiology School of Medical Sciences University of Adelaide Adelaide, South Australia, Australia.
authors.forename: Jennifer E
authors.initials: JE
authors.lastname: Hardingham