The DOI matches its Crossref record; 6 of the 6 references it cites were found in a registry or an index.
Genomic and Functional Fidelity of Small Cell Lung Cancer Patient-Derived Xenografts
Open accessAbstract
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-naïve 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. Cancer Discov; 8(5); 600–15. ©2018 AACR. This article is highlighted in the In This Issue feature, p. 517
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Subramanian, A., Tamayo, P., Mootha, V. K., Mukherjee, S., Ebert, B. L., Gillette, M. A., Paulovich, A., Pomeroy, S. L., Golub, T. R., Lander, E. S., et al. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0506580102 · Cited by 53,625
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Liberzon, A., Birger, C., Thorvaldsdóttir, H., Ghandi, M., Mesirov, J. P., & Tamayo, P. (2015) · Cell Systems · doi:10.1016/j.cels.2015.12.004 · Cited by 13,807
Genotypic and Histological Evolution of Lung Cancers Acquiring Resistance to EGFR Inhibitors
Sequist, L. V., Waltman, B. A., Dias-Santagata, D., Digumarthy, S., Turke, A. B., Fidias, P., Bergethon, K., Shaw, A. T., Gettinger, S., Cosper, A. K., et al. (2011) · Science Translational Medicine · doi:10.1126/scitranslmed.3002003 · Cited by 3,499
Self-citationTracking the Evolution of Non–Small-Cell Lung Cancer
Jamal-Hanjani, M., Wilson, G. A., McGranahan, N., Birkbak, N. J., Watkins, T. B. K., Veeriah, S., Shafi, S., Johnson, D. H., Mitter, R., Rosenthal, R., et al. (2017) · New England Journal of Medicine · doi:10.1056/nejmoa1616288 · Cited by 2,349
Gao, H., Korn, J. M., Ferretti, S., Monahan, J. E., Wang, Y., Singh, M., Zhang, C., Schnell, C., Yang, G., Zhang, Y., et al. (2015) · Nature Medicine · doi:10.1038/nm.3954 · Cited by 1,393
Faber, A. C., Farago, A. F., Costa, C., Dastur, A., Gomez-Caraballo, M., Robbins, R., Wagner, B. L., Rideout, W. M., Jakubik, C. T., Ham, J., et al. (2015) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1411848112 · Cited by 127
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Molecular subtypes of small cell lung cancer: a synthesis of human and mouse model data
Rudin, C. M., Poirier, J. T., Byers, L. A., Dive, C., Dowlati, A., George, J., Heymach, J. V., Johnson, J. E., Lehman, J. M., MacPherson, D., et al. (2019) · Nature Reviews Cancer · doi:10.1038/s41568-019-0133-9 · Cited by 1,254
Self-citationUnravelling tumour heterogeneity by single-cell profiling of circulating tumour cells
Keller, L., & Pantel, K. (2019) · Nature Reviews Cancer · doi:10.1038/s41568-019-0180-2 · Cited by 544
Applications of patient-derived tumor xenograft models and tumor organoids
Yoshida, G. J. (2020) · Journal of Hematology & Oncology · doi:10.1186/s13045-019-0829-z · Cited by 471
Lung Cancers: Molecular Characterization, Clonal Heterogeneity and Evolution, and Cancer Stem Cells
Testa, U., Castelli, G., & Pelosi, E. (2018) · Cancers · doi:10.3390/cancers10080248 · Cited by 403
Megyesfalvi, Z., Gay, C. M., Popper, H., Pirker, R., Ostoros, G., Heeke, S., Lang, C., Hoetzenecker, K., Schwendenwein, A., Boettiger, K., et al. (2023) · CA: A Cancer Journal for Clinicians · doi:10.3322/caac.21785 · Cited by 369
Metadata
- Authors
- Drapkin, B. J., George, J., Christensen, C. L., Mino-Kenudson, M., Dries, R., Sundaresan, T., Phat, S., Myers, D. T., Zhong, J., Igo, P., Hazar-Rethinam, M. H., Licausi, J. A., Gomez-Caraballo, M., Kem, M., Jani, K. N., Azimi, R., Abedpour, N., Menon, R., Lakis, S., Heist, R. S., Büttner, R., Haas, S., Sequist, L. V., Shaw, A. T., Wong, K.-K., Hata, A. N., Toner, M., Maheswaran, S., Haber, D. A., Peifer, M., Dyson, N., Thomas, R. K., & Farago, A. F.
- Venue
- Cancer Discovery
- Published
- 2018-04-30
- Volume
- 8
- Issue
- 5
- Pages
- 600-615
- ISSN
- 2159-8274 (ISSN-L)
- 2159-8290
- OpenAlex
- W2792474117
- Cited by
- 210
- References
- 6
- FWCI
- 7.92
- Type
- journal article
- Language
- en
- Open access
- green
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- The paper
- Drapkin, B. J., George, J., Christensen, C. L., Mino-Kenudson, M., Dries, R., Sundaresan, T., Phat, S., Myers, D. T., Zhong, J., Igo, P., Hazar-Rethinam, M. H., Licausi, J. A., Gomez-Caraballo, M., Kem, M., Jani, K. N., Azimi, R., Abedpour, N., Menon, R., Lakis, S., . . . Farago, A. F. (2018). Genomic and Functional Fidelity of Small Cell Lung Cancer Patient-Derived Xenografts. Cancer Discovery. https://doi.org/10.1158/2159-8290.cd-17-0935
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
