Patient-derived first generation xenografts of non-small cell lung cancers: promising tools for predicting drug responses for personalized chemotherapy.

TitlePatient-derived first generation xenografts of non-small cell lung cancers: promising tools for predicting drug responses for personalized chemotherapy.
Publication TypeJournal Article
Year of Publication2010
AuthorsDong, X, Guan, J, English, JC, Flint, J, Yee, J, Evans, K, Murray, N, Macaulay, C, Ng, RT, Gout, PW, Lam, WL, Laskin, J, Ling, V, Lam, S, Wang, Y
JournalClin Cancer Res
Volume16
Issue5
Pagination1442-51
Date Published2010 Mar 1
ISSN1078-0432
KeywordsAnimals, Antineoplastic Combined Chemotherapy Protocols, Carcinoma, Non-Small-Cell Lung, Cisplatin, Deoxycytidine, Humans, Individualized Medicine, Lung Neoplasms, Mice, Mice, Inbred NOD, Mice, SCID, Taxoids, Vinblastine, Xenograft Model Antitumor Assays
Abstract

PURPOSE: 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.

EXPERIMENTAL DESIGN: 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

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.

DOI10.1158/1078-0432.CCR-09-2878
Alternate JournalClin. Cancer Res.
PubMed ID20179238