title: Adaptation of a chemosensitivity assay to accurately assess pemetrexed in ex vivo cultures of lung cancer.
abstract: OBJECTIVE
  Pemetrexed is the only FDA approved treatment for mesothelioma and is a second line agent for treatment of non-small cell lung carcinoma (NSCLC). Pemetrexed is inhibited by folate and its analogs, which are components of many culture media, making it challenging to study pemetrexed in vitro. In order to accurately evaluate pemetrexed's effects in vitro, the protocol for a standard chemosensitivity assay, the ChemoFx drug response marker, had to be modified.
  
  
  METHODS
  Novel rinse and media change steps were assessed and then added to the assay protocol in order to observe pemetrexed activity. The intraday and interday stability of pemetrexed were also established under the adapted protocol. Then, the modified protocol was used to examine pemetrexed in 65 ex vivo lung cancer specimens.
  
  
  RESULTS
  Substituting 5% RPMI + EGF for BEGM allowed pemetrexed to exert its anticancer activity in the ChemoFx DRM. ChemoFx classified 6.2% of the lung specimens as responsive, 9.2% as intermediate responsive and 84.6% as non-responsive to pemetrexed.
  
  
  CONCLUSIONS
  Adapting the ChemoFx protocol allowed for the accurate evaluation of pemetrexed anticancer activity in ex vivo lung specimens. ChemoFx evaluation may provide an indication of a patient's clinical response to the drug prior to pemetrexed treatment. Having this information when treatment options are being considered could avoid wasted time, unnecessary costs and needless side effects that are the result of an inappropriate chemotherapy regimen.
authors.affiliation: Precision Therapeutics, Pittsburgh, PA, USA.
authors.forename: Sarah L
authors.initials: SL
authors.lastname: Suchy
authors.forename: Rodney J
authors.initials: RJ
authors.lastname: Landreneau
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Schuchert
authors.forename: Dakun
authors.initials: D
authors.lastname: Wang
authors.forename: Paul R
authors.initials: PR
authors.lastname: Ervin
authors.forename: Stacey L
authors.initials: SL
authors.lastname: Brower
mesh_terms: D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology*; D002277:Carcinoma / Q000188:drug therapy*; D002470:Cell Survival / Q000187:drug effects; D003470:Culture Media; D019008:Drug Resistance, Neoplasm; D004354:Drug Screening Assays, Antitumor / Q000379:methods; D004355:Drug Stability; D005971:Glutamates / Q000494:pharmacology*; D006147:Guanine / Q000031:analogs & derivatives* / Q000494:pharmacology; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy*; D000068437:Pemetrexed; D014407:Tumor Cells, Cultured
chemical_list: D000964:Antimetabolites, Antineoplastic; D003470:Culture Media; D005971:Glutamates; D000068437:Pemetrexed; D006147:Guanine