title: Patient-derived first generation xenografts of non-small cell lung cancers: promising tools for predicting drug responses for personalized chemotherapy.
abstract: OBJECTIVE
  Current chemotherapeutic regimens have only modest benefit for non-small cell lung cancer (NSCLC) patients. Cumulative toxicities/drug resistance limit chemotherapy given after the first-line regimen. For personalized chemotherapy, clinically relevant NSCLC models are needed for quickly predicting the most effective regimens for therapy with curative intent. In this study, first generation subrenal capsule xenografts of primary NSCLCs were examined for (a) determining responses to conventional chemotherapeutic regimens and (b) selecting regimens most effective for individual patients.
  
  
  METHODS
  Pieces (1x3x3 mm(3)) of 32 nontreated, completely resected patients' NSCLCs were grafted under renal capsules of nonobese diabetic/severe combined immunodeficient mice and treated with (A) cisplatin+vinorelbine, (B) cisplatin+docetaxel, (C) cisplatin+gemcitabine, and positive responses (treated tumor area <or=50% of control, P < 0.05) were determined. Clinical outcomes of treated patients were acquired.
  
  
  RESULTS
  Xenografts from all NSCLCs were established (engraftment rate, 90%) with the retention of major biological characteristics of the original cancers. The entire process of drug assessment took 8 weeks. Response rates to regimens A, B, and C were 28% (9 of 32), 42% (8 of 19), and 44% (7 of 16), respectively. Certain cancers that were resistant to a particular regimen were sensitive to others. The majority of responsive tumors contained foci of nonresponding cancer cells, indicative of tumor heterogeneity and potential drug resistance. Xenografts from six of seven patients who developed recurrence/metastasis were nonresponsive.
  
  
  CONCLUSIONS
  Models based on first generation NSCLC subrenal capsule xenografts have been developed, which are suitable for quick assessment (6-8 weeks) of the chemosensitivity of patients' cancers and selection of the most effective regimens. They hold promise for application in personalized chemotherapy of NSCLC patients.
authors.affiliation: Department of Cancer Endocrinology, BC Cancer Agency, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Xin
authors.initials: X
authors.lastname: Dong
authors.forename: Jun
authors.initials: J
authors.lastname: Guan
authors.forename: John C
authors.initials: JC
authors.lastname: English
authors.forename: Julia
authors.initials: J
authors.lastname: Flint
authors.forename: John
authors.initials: J
authors.lastname: Yee
authors.forename: Kenneth
authors.initials: K
authors.lastname: Evans
authors.forename: Nevin
authors.initials: N
authors.lastname: Murray
authors.forename: Calum
authors.initials: C
authors.lastname: Macaulay
authors.forename: Raymond T
authors.initials: RT
authors.lastname: Ng
authors.forename: Peter W
authors.initials: PW
authors.lastname: Gout
authors.forename: Wan L
authors.initials: WL
authors.lastname: Lam
authors.forename: Janessa
authors.initials: J
authors.lastname: Laskin
authors.forename: Victor
authors.initials: V
authors.lastname: Ling
authors.forename: Stephen
authors.initials: S
authors.lastname: Lam
authors.forename: Yuzhuo
authors.initials: Y
authors.lastname: Wang
mesh_terms: D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000473:pathology; D002945:Cisplatin / Q000008:administration & dosage; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D000077143:Docetaxel; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D057285:Precision Medicine / Q000379:methods*; D043823:Taxoids / Q000008:administration & dosage; D014747:Vinblastine / Q000008:administration & dosage / Q000031:analogs & derivatives; D000077235:Vinorelbine; D023041:Xenograft Model Antitumor Assays / Q000379:methods*; D000093542:Gemcitabine
chemical_list: D043823:Taxoids; D003841:Deoxycytidine; D000077143:Docetaxel; D014747:Vinblastine; D002945:Cisplatin; D000077235:Vinorelbine; D000093542:Gemcitabine