title: Benchmarking of gastric cancer sensitivity to anti-cancer drugs ex vivo as a basis for drug selection in systemic and intraperitoneal therapy.
abstract: BACKGROUND
  The choice of drugs for treatment of advanced gastric cancer (GC) is empirical. The purpose of the current study was to benchmark ex vivo the sensitivity of GC tumor cells from patients to standard cytotoxic and some newly introduced targeted drugs (TDs), as a basis for drug selection in the treatment of GC.
  
  
  METHODS
  Tumor cell samples from patients with GC were analyzed for sensitivity to 5-fluorouracil, cisplatin, oxaliplatin, irinotecan, mitomycin C, doxorubicin and docetaxel as well as for the targeted drugs bortezomib, sorafenib, sunitinib and rapamycin using a short-term in vitro assay based on retention of viable tumor cells of fluorescent fluorescein. Samples of normal mononuclear cells, chronic lymphocytic leukemia, ovarian cancer and colorectal cancer were included for comparison.
  
  
  RESULTS
  The GC samples were essentially as sensitive to the standard drugs and the TDs as those from colorectal cancer whereas the ovarian cancer samples were more sensitive. The individual GC samples varied considerably in sensitivity to increasing concentrations of the clinically used standard drugs. In GC, cisplatin was cross-resistant to oxaliplatin and 5-fluorouracil which, on the other hand, was not cross-resistant to the other cytotoxic drugs. The activity of sunitinib did not obviously correlate to that of the standard drugs.
  
  
  CONCLUSIONS
  Ex vivo assessment of drug sensitivity of tumor cells from patients with GC is feasible and may provide information that could be useful for selection of drugs for treatment. Drug sensitivity varies considerably between and within individual samples arguing for individualized selection of drugs for chemotherapy.
authors.affiliation: Department of Surgical Sciences, Uppsala University, Uppsala, Sweden. bo.hultman@ltdalarna.se.
authors.forename: Bo
authors.initials: B
authors.lastname: Hultman
authors.affiliation: Department of Surgical Sciences, Uppsala University, Uppsala, Sweden. haile.mahteme@surgsci.uu.se.
authors.forename: Haile
authors.initials: H
authors.lastname: Mahteme
authors.affiliation: Department of Surgical Sciences, Uppsala University, Uppsala, Sweden. magnus.sundbom@surgsci.uu.se.
authors.forename: Magnus
authors.initials: M
authors.lastname: Sundbom
authors.affiliation: Surgery Department, Västmanlands Hospital, SE-721 89, Västerås, Sweden. martin.ljungman@ltvastmanland.se.
authors.forename: Martin
authors.initials: M
authors.lastname: Ljungman
authors.affiliation: Department of Medical Sciences, Uppsala University, Uppsala, Sweden. rolf.larsson@medsci.uu.se.
authors.forename: Rolf
authors.initials: R
authors.lastname: Larsson
authors.affiliation: Department of Radiology, Oncology and Radiation Sciences, Uppsala University, SE-751 85, Uppsala, Sweden. peter.nygren@medsci.uu.se.
authors.forename: Peter
authors.initials: P
authors.lastname: Nygren
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D019985:Benchmarking / Q000592:standards*; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor / Q000592:standards*; D005240:Feasibility Studies; D005260:Female; D006801:Humans; D008297:Male; D008495:Medical Oncology / Q000592:standards*; D008875:Middle Aged; D058990:Molecular Targeted Therapy / Q000592:standards*; D018579:Patient Selection; D011237:Predictive Value of Tests; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000473:pathology; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents