Drapkin, Benjamin J., George, Julie, Christensen, Camilla L., Mino-Kenudson, Mari, Dries, Ruben ORCID: 0000-0001-7650-7754, Sundaresan, Tilak, Phat, Sarah, Myers, David T., Zhong, Jun, Igo, Peter, Hazar-Rethinam, Mehlika H., Licausi, Joseph A., Gomez-Caraballo, Maria, Kem, Marina, Jani, Kandarp N., Azimi, Roxana, Abedpour, Nima, Menon, Roopika, Lakis, Sotirios, Heist, Rebecca S., Buettner, Reinhard, Haas, Stefan ORCID: 0000-0003-3418-3688, Sequist, Lecia V., Shaw, Alice T., Wong, Kwok-Kin, Hata, Aaron N., Toner, Mehmet, Maheswaran, Shyamala, Haber, Daniel A., Peifer, Martin, Dyson, Nicholas, Thomas, Roman K. and Farago, Anna F. (2018). Genomic and Functional Fidelity of Small Cell Lung Cancer Patient-Derived Xenografts. Cancer Discov., 8 (5). S. 600 - 616. PHILADELPHIA: AMER ASSOC CANCER RESEARCH. ISSN 2159-8290

Full text not available from this repository.

Abstract

Small cell lung cancer (SCLC) patient-derived xenografts (PDX) can be generated from biopsies or circulating tumor cells (CTC), though scarcity of tissue and low efficiency of tumor growth have previously limited these approaches. Applying an established clinical-translational pipeline for tissue collection and an automated microfluidic platform for CTC enrichment, we generated 17 biopsy-derived PDXs and 17 CTC-derived PDXs in a 2-year timeframe, at 89% and 38% efficiency, respectively. Whole-exome sequencing showed that somatic alterations are stably maintained between patient tumors and PDXs. Early-passage PDXs maintain the genomic and transcriptional profiles of the founder PDX. In vivo treatment with etoposide and platinum (EP) in 30 PDX models demonstrated greater sensitivity in PDXs from EP-naive patients, and resistance to EP corresponded to increased expression of a MYC gene signature. Finally, serial CTC-derived PDXs generated from an individual patient at multiple time points accurately recapitulated the evolving drug sensitivities of that patient's disease. Collectively, this work highlights the translational potential of this strategy. SIGNIFICANCE: Effective translational research utilizing SCLC PDX models requires both efficient generation of models from patients and fidelity of those models in representing patient tumor characteristics. We present approaches for efficient generation of PDXs from both biopsies and CTCs, and demonstrate that these models capture the mutational landscape and functional features of the donor tumors. (C) 2018 AACR.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Drapkin, Benjamin J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
George, JulieUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Christensen, Camilla L.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Mino-Kenudson, MariUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Dries, RubenUNSPECIFIEDorcid.org/0000-0001-7650-7754UNSPECIFIED
Sundaresan, TilakUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Phat, SarahUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Myers, David T.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Zhong, JunUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Igo, PeterUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hazar-Rethinam, Mehlika H.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Licausi, Joseph A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Gomez-Caraballo, MariaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kem, MarinaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Jani, Kandarp N.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Azimi, RoxanaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Abedpour, NimaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Menon, RoopikaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lakis, SotiriosUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Heist, Rebecca S.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Buettner, ReinhardUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Haas, StefanUNSPECIFIEDorcid.org/0000-0003-3418-3688UNSPECIFIED
Sequist, Lecia V.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Shaw, Alice T.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wong, Kwok-KinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hata, Aaron N.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Toner, MehmetUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Maheswaran, ShyamalaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Haber, Daniel A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Peifer, MartinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Dyson, NicholasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Thomas, Roman K.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Farago, Anna F.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-186803
DOI: 10.1158/2159-8290.CD-17-0935
Journal or Publication Title: Cancer Discov.
Volume: 8
Number: 5
Page Range: S. 600 - 616
Date: 2018
Publisher: AMER ASSOC CANCER RESEARCH
Place of Publication: PHILADELPHIA
ISSN: 2159-8290
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
CIRCULATING TUMOR-CELLS; METASTATIC COLORECTAL-CANCER; SET ENRICHMENT ANALYSIS; PLUS ETOPOSIDE; PHASE-III; GENE; HETEROGENEITY; EXPRESSION; ABNORMALITIES; PROGRESSIONMultiple languages
OncologyMultiple languages
Refereed: Yes
URI: http://kups.ub.uni-koeln.de/id/eprint/18680

Downloads

Downloads per month over past year

Altmetric

Export

Actions (login required)

View Item View Item