title: Reliability of tumor primary cultures as a model for drug response prediction: expression profiles comparison of tissues versus primary cultures from colorectal cancer patients.
abstract: OBJECTIVE
  Since primary tumor cells from patients have been used as a model for assessment of drug response for individual patients, this study aims to evaluate the reliability of such a model in colorectal cancer (CRC) in predicting the response of tumor tissues through comparison of their expression profiles.
  
  
  METHODS
  Establishment of primary cultures from tissues obtained surgically from CRC patients allowed us to study the gene expression differences between normal and tumor tissues as well as primary cultures derived from the tumor mass. The tissues comparison highlights the molecular characteristics of tumors, while the comparison between primary tumor cells versus normal and tumor tissues allowed us to identify alterations associated with the establishment of culture. Genes-drug association analyses allowed us to fine-tune our expectations while using primary culture as a model for drug assessment.
  
  
  RESULTS
  Comparison between tumor cultures and original tissues through functional analyses showed the deregulations caused by culture establishment. Investigating the impact of such changes in genes-drug associations to identify the potential alterations in drug response, we found that primary cultures may have increased susceptibility toward paclitaxel, but reduced susceptibility toward analogues of fluorouracil compared with original tumors.
  
  
  CONCLUSIONS
  Response of primary tumor cells toward different drugs is not linearly associated to tumor tissues. Our results highlight the importance to account for the discrepancy in responses between the primary tumor cells and original counterparts in order to provide clinicians with important insights to improve selection of drugs for individual patients based on in vitro assays.
authors.affiliation: Cancer Science Institute of Singapore, National University of Singapore, 28 Medical Drive #02-07, Singapore 117456, Singapore. phsglb@nus.edu.sg
authors.forename: Gregory Lucien
authors.initials: GL
authors.lastname: Bellot
authors.forename: Wei Han
authors.initials: WH
authors.lastname: Tan
authors.forename: Ling Lee
authors.initials: LL
authors.lastname: Tay
authors.forename: Dean
authors.initials: D
authors.lastname: Koh
authors.forename: Xueying
authors.initials: X
authors.lastname: Wang
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology; D002166:Camptothecin / Q000031:analogs & derivatives / Q000494:pharmacology; D000069287:Capecitabine; D002945:Cisplatin / Q000494:pharmacology; D015179:Colorectal Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism*; D003841:Deoxycytidine / Q000031:analogs & derivatives / Q000494:pharmacology; D015536:Down-Regulation / Q000187:drug effects; D004317:Doxorubicin / Q000494:pharmacology; D005047:Etoposide / Q000494:pharmacology; D005467:Floxuridine / Q000494:pharmacology; D005455:Fluorescent Antibody Technique; D005472:Fluorouracil / Q000031:analogs & derivatives / Q000494:pharmacology; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D042822:Genomic Instability / Q000187:drug effects; D006801:Humans; D000077146:Irinotecan; D008677:Metaphase; D017239:Paclitaxel / Q000494:pharmacology; D016133:Polymerase Chain Reaction; D011237:Predictive Value of Tests; D040081:Protein Array Analysis; D015203:Reproducibility of Results; D005641:Tegafur / Q000494:pharmacology; D046888:Tissue Array Analysis; D014407:Tumor Cells, Cultured / Q000187:drug effects*; D015854:Up-Regulation / Q000187:drug effects; D014498:Uracil / Q000494:pharmacology
chemical_list: D000970:Antineoplastic Agents; D005467:Floxuridine; D003841:Deoxycytidine; D005641:Tegafur; D014498:Uracil; D000069287:Capecitabine; D005047:Etoposide; D000077146:Irinotecan; D004317:Doxorubicin; D017239:Paclitaxel; D002945:Cisplatin; D005472:Fluorouracil; C025034:doxifluridine; D002166:Camptothecin