Tumor Xenografts of Human Clear Cell Renal Cell Carcinoma But Not Corresponding Cell Lines Recapitulate Clinical Response to Sunitinib: Feasibility of Using Biopsy Samples

Yiyu Dong, Brandon J. Manley, Maria F. Becerra, Almedina Redzematovic, Jozefina Casuscelli, Daniel M. Tennenbaum, Ed Reznik, Song Han, Nicole Benfante, Ying Bei Chen, Maria E. Arcila, Omer Aras, Martin H. Voss, Darren R. Feldman, Robert J. Motzer, Nicola Fabbri, John H. Healey, Patrick J. Boland, Mohit Chawla, Jeremy C. DurackChung Han Lee, Jonathan A. Coleman, Paul Russo, A. Ari Hakimi, Emily H. Cheng, James J. Hsieh

Research output: Contribution to journalArticle

13 Scopus citations

Abstract

Background: Parallel development of preclinical models that recapitulate treatment response observed in patients is central to the advancement of personalized medicine. Objective: To evaluate the use of biopsy specimens to develop patient-derived xenografts and the use of corresponding cell lines from renal cell carcinoma (RCC) tumors for the assessment of histopathology, genomics, and treatment response. Design, setting, and participants: A total of 74 tumor specimens from 66 patients with RCC were implanted into immunocompromised NOD-SCID IL2Rg−/− mice. Four cell lines generated from patients’ specimens with clear cell pathology were used for comparative studies. Outcome measurements and statistical analysis: Preclinical models were established and assessed. Engraftment rates were analyzed using chi-square testing. Analysis of variance (two-way analysis of variance) was conducted to assess tumor growth. Results and limitations: Overall, 33 RCC mouse xenograft models were generated with an overall engraftment rate of 45% (33 of 74). Tumor biopsies engrafted comparably with surgically resected tumors (58% vs 41%; p = 0.3). Xenograft tumors and their original tumors showed high fidelity in regard to histology, mutation status, copy number change, and targeted therapy response. Engraftment rates from metastatic tumors were higher but not more significant than primary tumors (54% vs 34%; p = 0.091). Our engraftment rate using metastases or biopsies was comparable with recent reports using resected primary tumors. In stark contrast to corresponding cell lines, all tested xenografts recapitulated patients’ clinical response to sunitinib. Conclusions: Patient-derived xenograft models can be effectively established from tumor biopsies. Preclinical xenograft models but not matched cell lines reflected clinical responses to sunitinib. Patient summary: Matched patient-derived clear cell renal cell carcinoma xenografts and cell lines from responsive and refractory patients treated with sunitinib were established and evaluated for pharmacologic response to anti–vascular endothelial growth factor treatment. Both models accurately reflected the genetic characteristics of original tumors, but only xenografts recapitulated drug responses observed in patients. These models could serve as a powerful platform for precision medicine. Patient-derived xenograft models can be effectively established from tumor biopsies. Preclinical xenograft models but not matched cell lines reflected clinical responses to sunitinib.

Original languageEnglish
Pages (from-to)590-598
Number of pages9
JournalEuropean Urology Focus
Volume3
Issue number6
DOIs
StatePublished - Dec 2017
Externally publishedYes

Keywords

  • Biopsy
  • Cancer cell lines
  • Patient-derived xenografts
  • Precision medicine
  • Preclinical studies
  • Renal cell carcinoma
  • Sunitinib

Fingerprint Dive into the research topics of 'Tumor Xenografts of Human Clear Cell Renal Cell Carcinoma But Not Corresponding Cell Lines Recapitulate Clinical Response to Sunitinib: Feasibility of Using Biopsy Samples'. Together they form a unique fingerprint.

  • Cite this

    Dong, Y., Manley, B. J., Becerra, M. F., Redzematovic, A., Casuscelli, J., Tennenbaum, D. M., Reznik, E., Han, S., Benfante, N., Chen, Y. B., Arcila, M. E., Aras, O., Voss, M. H., Feldman, D. R., Motzer, R. J., Fabbri, N., Healey, J. H., Boland, P. J., Chawla, M., ... Hsieh, J. J. (2017). Tumor Xenografts of Human Clear Cell Renal Cell Carcinoma But Not Corresponding Cell Lines Recapitulate Clinical Response to Sunitinib: Feasibility of Using Biopsy Samples. European Urology Focus, 3(6), 590-598. https://doi.org/10.1016/j.euf.2016.08.005