title: An in vitro chemoresponse assay defines a subset of colorectal and lung carcinomas responsive to cetuximab.
abstract: Cetuximab is a chimeric monoclonal antibody for the epidermal growth factor receptor (EGFR) that may provide benefit to select cancer patients; however, identification of the characteristics of those patients who may benefit from its use is not complete. The ChemoFx® drug response marker (DRM) is an in vitro assay that can provide drug response data on tumor specimens before any patient treatment is initiated. We determined the feasibility of using the ChemoFx DRM to test tumor samples for sensitivity to cetuximab. We exposed four non-small cell lung carcinoma (NSCLC) cell lines (H358, H520, HCC827, and H1666) to cetuximab and determined their sensitivity using the ChemoFx DRM and, in parallel, EGFR status using immunocytochemistry, Western blotting, and In-Cell Western (TM) analysis. We used the ChemoFx DRM to determine cetuximab sensitivity of primary NSCLC and colorectal tumor samples. The ChemoFx DRM distinguished between cetuximab-sensitive and -resistant cell lines. Cetuximab sensitivity was not dependent on EGFR mutational status; H358 cells were non-responsive to cetuximab yet contain wild-type EGFR, whereas H1666 cells were intermediately responsive to cetuximab and contain wild-type EGFR. HCC827 (EGFR-mutant) cells were intermediately responsive and, as expected, H520 cells (EGFR-null) were non-responsive to cetuximab. ChemoFx-determined cetuximab sensitivity of primary NSCLC and colorectal tumor samples was 9.0% and 7.5%, respectively. Use of the ChemoFx DRM is feasible for determining cetuximab sensitivity. The ChemoFx-determined cetuximab responses of primary NSCLC and colorectal tumor specimens were similar to published response rates of patients to treatment with cetuximab monotherapy.
authors.affiliation: Precision Therapeutics Inc., Pittsburgh, PA, USA.
authors.forename: Shara D
authors.initials: SD
authors.lastname: Rice
authors.forename: Theresa R
authors.initials: TR
authors.lastname: Cassino
authors.forename: Lahari
authors.initials: L
authors.lastname: Sakhamuri
authors.forename: Nan
authors.initials: N
authors.lastname: Song
authors.forename: Karl E
authors.initials: KE
authors.lastname: Williams
authors.forename: Stacey L
authors.initials: SL
authors.lastname: Brower
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy; D000077192:Adenocarcinoma of Lung; D000911:Antibodies, Monoclonal / Q000235:genetics / Q000627:therapeutic use*; D001681:Biological Assay; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000235:genetics / Q000473:pathology; D002461:Cell Line, Transformed; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000188:drug therapy / Q000235:genetics; D004354:Drug Screening Assays, Antitumor / Q000379:methods*; D066246:ErbB Receptors / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D005240:Feasibility Studies; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy; D009154:Mutation / Q000235:genetics; D009369:Neoplasms / Q000188:drug therapy* / Q000235:genetics; D012680:Sensitivity and Specificity
chemical_list: D000911:Antibodies, Monoclonal; D066246:ErbB Receptors