title: Unexpected effect of the monoclonal antibody Panitumumab on human cancer cells with different KRAS status.
abstract: Panitumumab is the first fully human monoclonal antibody targeting the epidermal growth factor receptor whose clinical use is limited to patients with a non-mutated KRAS status. The aim of this in vitro study was to evaluate whether the KRAS status might influence the cytotoxic and radiosensitizing efficacy of Panitumumab. Exponentially growing cancer cells (HT-29: KRAS wild-type, A549: KRAS mutant) were either treated with the monoclonal antibody alone in growth and proliferation assays or in combination with radiation in metabolic and colony-forming assays. For the assessment of ionizing radiation-induced DNA damage and to evaluate Panitumumab's influence on DNA damage repair, the γH2AX foci assay was performed. Treatment with Panitumumab resulted in a concentration-independent growth inhibition as well as a cytotoxic effect only in the KRAS-mutated cell line A549. BrdU assay confirmed an antiproliferative influence of Panitumumab. When combined with irradiation, incubation with the antibody was found to result in an enhanced radiosensitivity. Contrary to expectations, Panitumumab had no influence on the cell growth, LDH release or clonogenic survival of KRAS wild-type cells HT-29. Our results suggest that response to Panitumumab treatment is not only controlled by the KRAS status but may also be essentially influenced by other regulating factors.
authors.affiliation: Department of Radiotherapy and Radiation Oncology, University of Rostock, Südring 75, 18059 Rostock, Germany.
authors.forename: Nina
authors.initials: N
authors.lastname: Tiemann
authors.forename: Guido
authors.initials: G
authors.lastname: Hildebrandt
authors.forename: Katrin
authors.initials: K
authors.lastname: Manda
mesh_terms: D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000494:pharmacology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004260:DNA Repair / Q000187:drug effects / Q000235:genetics; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D066246:ErbB Receptors / Q000037:antagonists & inhibitors; D019073:HT29 Cells; D006801:Humans; D009154:Mutation; D000077544:Panitumumab; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins / Q000235:genetics*
chemical_list: D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; C117307:KRAS protein, human; D011518:Proto-Oncogene Proteins; D000077544:Panitumumab; D066246:ErbB Receptors; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins