Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Oncology Letters
      • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Biomedical Reports
      • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • Information for Authors
    • Information for Reviewers
    • Information for Librarians
    • Information for Advertisers
    • Conferences
  • Language Editing
Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • For Authors
    • For Reviewers
    • For Librarians
    • For Advertisers
    • Conferences
  • Language Editing
Login Register Submit
  • This site uses cookies
  • You can change your cookie settings at any time by following the instructions in our Cookie Policy. To find out more, you may read our Privacy Policy.

    I agree
Search articles by DOI, keyword, author or affiliation
Search
Advanced Search
presentation
Oncology Reports
Join Editorial Board Propose a Special Issue
Print ISSN: 1021-335X Online ISSN: 1791-2431
Journal Cover
October-2021 Volume 46 Issue 4

Full Size Image

Sign up for eToc alerts
Recommend to Library

Journals

International Journal of Molecular Medicine

International Journal of Molecular Medicine

International Journal of Molecular Medicine is an international journal devoted to molecular mechanisms of human disease.

International Journal of Oncology

International Journal of Oncology

International Journal of Oncology is an international journal devoted to oncology research and cancer treatment.

Molecular Medicine Reports

Molecular Medicine Reports

Covers molecular medicine topics such as pharmacology, pathology, genetics, neuroscience, infectious diseases, molecular cardiology, and molecular surgery.

Oncology Reports

Oncology Reports

Oncology Reports is an international journal devoted to fundamental and applied research in Oncology.

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine is an international journal devoted to laboratory and clinical medicine.

Oncology Letters

Oncology Letters

Oncology Letters is an international journal devoted to Experimental and Clinical Oncology.

Biomedical Reports

Biomedical Reports

Explores a wide range of biological and medical fields, including pharmacology, genetics, microbiology, neuroscience, and molecular cardiology.

Molecular and Clinical Oncology

Molecular and Clinical Oncology

International journal addressing all aspects of oncology research, from tumorigenesis and oncogenes to chemotherapy and metastasis.

World Academy of Sciences Journal

World Academy of Sciences Journal

Multidisciplinary open-access journal spanning biochemistry, genetics, neuroscience, environmental health, and synthetic biology.

International Journal of Functional Nutrition

International Journal of Functional Nutrition

Open-access journal combining biochemistry, pharmacology, immunology, and genetics to advance health through functional nutrition.

International Journal of Epigenetics

International Journal of Epigenetics

Publishes open-access research on using epigenetics to advance understanding and treatment of human disease.

Medicine International

Medicine International

An International Open Access Journal Devoted to General Medicine.

Journal Cover
October-2021 Volume 46 Issue 4

Full Size Image

Sign up for eToc alerts
Recommend to Library

  • Article
  • Citations
    • Cite This Article
    • Download Citation
    • Create Citation Alert
    • Remove Citation Alert
    • Cited By
  • Similar Articles
    • Related Articles (in Spandidos Publications)
    • Similar Articles (Google Scholar)
    • Similar Articles (PubMed)
  • Download PDF
  • Download XML
  • View XML
Article Open Access

Development of patient‑derived tumor organoids and a drug testing model for renal cell carcinoma

  • Authors:
    • Akira Kazama
    • Tsutomu Anraku
    • Hiroo Kuroki
    • Yuko Shirono
    • Masaki Murata
    • Vladimir Bilim
    • Andrey Ugolkov
    • Kazuhide Saito
    • Yoshihiko Tomita
  • View Affiliations / Copyright

    Affiliations: Department of Urology, Division of Molecular Oncology, Niigata University Graduate School of Medical and Dental Sciences, Niigata 951‑8510, Japan, Actuate Therapeutics, Inc., Fort Worth, TX 76107, USA
    Copyright: © Kazama et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 226
    |
    Published online on: September 1, 2021
       https://doi.org/10.3892/or.2021.8177
  • Expand metrics +
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )
Cited By (CrossRef): 0 citations Loading Articles...

This article is mentioned in:



Abstract

The selection of effective therapeutic agents is critical for improving the survival of patients with renal cell carcinoma (RCC). The aim of the present study was to develop an ex vivo drug testing assay using patient‑derived tumor organoid (TO) cultures. For this purpose, surgical tumor specimens were obtained from 20 patients with RCC. TOs were developed ex vivo from freshly resected RCC tumors, and their histopathological and molecular characteristics were evaluated using histological staining and whole‑exome sequencing (WES). Using a cell viability assay, the therapeutic efficacy of standard of care tyrosine kinase inhibitors in RCC TOs was determined. It was found that TOs recapitulated the histological features of primary RCC tumors. Using WES, a strong concordance was identified at the genetic level between the primary tumors and their corresponding TOs. Using patient‑derived TO models, a prototype of an ex vivo drug testing assay was developed, and it was found that RCC TOs exhibited differential responses to sunitinib, pazopanib, cabozantinib, axitinib and sorafenib treatment. On the whole, although the predictive value of the current assay has to be tested and validated in future clinical studies, the findings of the present study demonstrate a novel approach for ex vivo drug testing in patient‑derived TO models, which may have potential for use in the personalized treatment of cancer patients.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

View References

1 

Kabaria R, Klaassen Z and Terris MK: Renal cell carcinoma: Links and risks. Int J Nephrol Renovasc Dis. 9:45–52. 2016.PubMed/NCBI

2 

Escudier B, Porta C, Schmidinger M, Rioux-Leclercq N, Bex A, Khoo V, Grünwald V, Gillessen S and Horwich A; ESMO Guidelines Committee. Electronic address, : clinicalguidelines@esmo.org: Renal cell carcinoma: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol. 30:706–720. 2019. View Article : Google Scholar : PubMed/NCBI

3 

Malone ER, Oliva M, Sabatini PJ, Stockley TL and Siu LL: Molecular profiling for precision cancer therapies. Genome Med. 12:82020. View Article : Google Scholar : PubMed/NCBI

4 

Fatehullah A, Tan SH and Barker N: Organoids as an in vitro model of human development and disease. Nat Cell Biol. 18:246–254. 2016. View Article : Google Scholar : PubMed/NCBI

5 

Clevers H: Modeling development and disease with organoids. Cell. 165:1586–1597. 2016. View Article : Google Scholar : PubMed/NCBI

6 

Rookmaaker MB, Schutgens F, Verhaar MC and Clevers H: Development and application of human adult stem or progenitor cell organoids. Nat Rev Nephrol. 11:546–554. 2015. View Article : Google Scholar : PubMed/NCBI

7 

Kapałczyńska M, Kolenda T, Przybyła W, Zajączkowska M, Teresiak A, Filas V, Ibbs M, Bliźniak R, Łuczewski Ł and Lamperska K: 2D and 3D cell cultures-a comparison of different types of cancer cell cultures. Arch Med Sci. 4:910–919. 2018.PubMed/NCBI

8 

Broutier L, Mastrogiovanni G, Verstegen MM, Francies HE, Gavarró LM, Bradshaw CR, Allen GE, Arnes-Benito R, Sidorova O, Gaspersz MP, et al: Human primary liver cancer-derived organoid cultures for disease modeling and drug screening. Nat Med. 12:1424–1435. 2017. View Article : Google Scholar : PubMed/NCBI

9 

Gao D, Vela I, Sboner A, Iaquinta PJ, Karthaus WR, Gopalan A, Dowling C, Wanjala JN, Undvall EA, Arora VK, et al: Organoid cultures derived from patients with advanced prostate cancer. Cell. 159:176–187. 2014. View Article : Google Scholar : PubMed/NCBI

10 

Ganesh K, Wu C, O'Rourke KP, Szeglin BC, Zheng Y, Sauvé CG, Adileh M, Wasserman I, Marco MR, Kim AS, et al: A rectal cancer organoid platform to study individual responses to chemoradiation. Nat Med. 25:1607–1614. 2019. View Article : Google Scholar : PubMed/NCBI

11 

Romero-Calvo I, Weber CR, Ray M, Brown M, Kirby K, Nandi RK, Long TM, Sparrow SM, Ugolkov A, Qiang W, et al: Human organoids share structural and genetic features with primary pancreatic adenocarcinoma tumors. Mol Cancer Res. 17:70–83. 2019. View Article : Google Scholar : PubMed/NCBI

12 

Saito Y, Muramatsu T, Kanai Y, Ojima H, Sukeda A, Hiraoka N, Arai E, Sugiyama Y, Matsuzaki J, Uchida R, et al: Establishment of patient-derived organoids and drug screening for biliary tract carcinoma. Cell Rep. 27:1265–1276.e4. 2019. View Article : Google Scholar : PubMed/NCBI

13 

Lee SH, Hu W, Matulay JT, Silva MV, Owczarek TB, Kim K, Chua CW, Barlow LJ, Kandoth C, Williams AB, et al: Tumor evolution and drug response in patient-derived organoid models of bladder cancer. Cell. 173:515–528.e17. 2018. View Article : Google Scholar : PubMed/NCBI

14 

Bilim V, Yuuki K, Itoi T, Muto A, Kato T, Nagaoka A, Motoyama T and Tomita Y: Double inhibition of XIAP and Bcl-2 axis is beneficial for retrieving sensitivity of renal cell cancer to apoptosis. Br J Cancer. 98:941–949. 2008. View Article : Google Scholar : PubMed/NCBI

15 

Liston DR and Davis M: Clinically relevant concentrations of anticancer drugs: A guide for nonclinical studies. Clin Cancer Res. 23:3489–3498. 2017. View Article : Google Scholar : PubMed/NCBI

16 

Kim M, Mun H, Sung CO, Cho EJ, Jeon HJ, Chun SM, Jung DJ, Shin TH, Jeong GS, Kim DK, et al: Patient-derived lung cancer organoids as in vitro cancer models for therapeutic screening. Nat Commun. 10:39912019. View Article : Google Scholar : PubMed/NCBI

17 

Aberle MR, Burkhart RA, Tiriac H, Olde Damink SW, Dejong CH, Tuveson DA and van Dam RM: Patient-derived organoid models help define personalized management of gastrointestinal cancer. Br J Surg. 105:e48–e60. 2018. View Article : Google Scholar : PubMed/NCBI

18 

van de Wetering M, Francies HE, Francis JM, Bounova G, Iorio F, Pronk A, van Houdt W, van Gorp J, Taylor-Weiner A, Kester L, et al: Prospective derivation of a living organoid biobank of colorectal cancer patients. Cell. 161:933–945. 2015. View Article : Google Scholar : PubMed/NCBI

19 

Grassi L, Alfonsi R, Francescangeli F, Signore M, De Angelis ML, Addario A, Costantini M, Flex E, Ciolfi A, Pizzi S, et al: Organoids as a new model for improving regenerative medicine and cancer personalized therapy in renal diseases. Cell Death Dis. 10:2012019. View Article : Google Scholar : PubMed/NCBI

20 

Neal JT, Li X, Zhu J, Giangarra V, Grzeskowiak CL, Ju J, Liu IH, Chiou SH, Salahudeen AA, Smith AR, et al: Organoid modeling of the tumor immune microenvironment. Cell. 175:1972–1988.e16. 2018. View Article : Google Scholar : PubMed/NCBI

21 

Vlachogiannis G, Hedayat S, Vatsiou A, Jamin Y, Fernández-Mateos J, Khan K, Lampis A, Eason K, Huntingford I, Burke R, et al: Patient-derived organoids model treatment response of metastatic gastrointestinal cancers. Science. 359:920–926. 2018. View Article : Google Scholar : PubMed/NCBI

22 

Bian S, Repic M, Guo Z, Kavirayani A, Burkard T, Bagley JA, Krauditsch C and Knoblich JA: Author correction: Genetically engineered cerebral organoids model brain tumor formation. Nat Methods. 15:7482018. View Article : Google Scholar : PubMed/NCBI

23 

Motzer RJ, Penkov K, Haanen J, Rini B, Albiges L, Campbell MT, Venugopal B, Kollmannsberger C, Negrier S, Uemura M, et al: Avelumab plus Axitinib versus Sunitinib for advanced renal-cell carcinoma. N Engl J Med. 380:1103–1115. 2019. View Article : Google Scholar : PubMed/NCBI

24 

Rini BI, Plimack ER, Stus V, Gafanov R, Hawkins R, Nosov D, Pouliot F, Alekseev B, Soulières D, Melichar B, et al: KEYNOTE-426 investigators. Pembrolizumab plus Axitinib versus Sunitinib for advanced renal-cell carcinoma. N Engl J Med. 380:1116–1127. 2019. View Article : Google Scholar : PubMed/NCBI

25 

Motzer RJ, Tannir NM, McDermott DF, Arén Frontera O, Melichar B, Choueiri TK, Plimack ER, Barthélémy P, Porta C, George S, et al: CheckMate 214 investigators. Nivolumab plus Ipilimumab versus Sunitinib in advanced renal-cell carcinoma. N Engl J Med. 378:1277–1290. 2018. View Article : Google Scholar : PubMed/NCBI

26 

Zerdes I, Tolia M, Tsoukalas N, Mitsis M, Kardamakis D, Pistevou-Gombaki K, Tsekeris P and Kyrgias G: Systemic therapy of metastatic renal cell carcinoma: Review of the current literature. Urologia. 86:3–8. 2019. View Article : Google Scholar : PubMed/NCBI

27 

Liu C, Qin T, Huang Y, Li Y, Chen G and Sun C: Drug screening model meets cancer organoid technology. Transl Oncol. 13:1008402020. View Article : Google Scholar : PubMed/NCBI

28 

Li M and Izpisua Belmonte JC: Organoids-preclinical models of human disease. N Engl J Med. 380:569–579. 2019. View Article : Google Scholar : PubMed/NCBI

29 

Bleijs M, van de Wetering M, Clevers H and Drost J: Xenograft and organoid model systems in cancer research. EMBO J. 38:e1016542019. View Article : Google Scholar : PubMed/NCBI

30 

Drost J and Clevers H: Organoids in cancer research. Nat Rev Cancer. 18:407–418. 2018. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Kazama A, Anraku T, Kuroki H, Shirono Y, Murata M, Bilim V, Ugolkov A, Saito K and Tomita Y: Development of patient‑derived tumor organoids and a drug testing model for renal cell carcinoma. Oncol Rep 46: 226, 2021.
APA
Kazama, A., Anraku, T., Kuroki, H., Shirono, Y., Murata, M., Bilim, V. ... Tomita, Y. (2021). Development of patient‑derived tumor organoids and a drug testing model for renal cell carcinoma. Oncology Reports, 46, 226. https://doi.org/10.3892/or.2021.8177
MLA
Kazama, A., Anraku, T., Kuroki, H., Shirono, Y., Murata, M., Bilim, V., Ugolkov, A., Saito, K., Tomita, Y."Development of patient‑derived tumor organoids and a drug testing model for renal cell carcinoma". Oncology Reports 46.4 (2021): 226.
Chicago
Kazama, A., Anraku, T., Kuroki, H., Shirono, Y., Murata, M., Bilim, V., Ugolkov, A., Saito, K., Tomita, Y."Development of patient‑derived tumor organoids and a drug testing model for renal cell carcinoma". Oncology Reports 46, no. 4 (2021): 226. https://doi.org/10.3892/or.2021.8177
Copy and paste a formatted citation
x
Spandidos Publications style
Kazama A, Anraku T, Kuroki H, Shirono Y, Murata M, Bilim V, Ugolkov A, Saito K and Tomita Y: Development of patient‑derived tumor organoids and a drug testing model for renal cell carcinoma. Oncol Rep 46: 226, 2021.
APA
Kazama, A., Anraku, T., Kuroki, H., Shirono, Y., Murata, M., Bilim, V. ... Tomita, Y. (2021). Development of patient‑derived tumor organoids and a drug testing model for renal cell carcinoma. Oncology Reports, 46, 226. https://doi.org/10.3892/or.2021.8177
MLA
Kazama, A., Anraku, T., Kuroki, H., Shirono, Y., Murata, M., Bilim, V., Ugolkov, A., Saito, K., Tomita, Y."Development of patient‑derived tumor organoids and a drug testing model for renal cell carcinoma". Oncology Reports 46.4 (2021): 226.
Chicago
Kazama, A., Anraku, T., Kuroki, H., Shirono, Y., Murata, M., Bilim, V., Ugolkov, A., Saito, K., Tomita, Y."Development of patient‑derived tumor organoids and a drug testing model for renal cell carcinoma". Oncology Reports 46, no. 4 (2021): 226. https://doi.org/10.3892/or.2021.8177
Follow us
  • Twitter
  • LinkedIn
  • Facebook
About
  • Spandidos Publications
  • Careers
  • Cookie Policy
  • Privacy Policy
How can we help?
  • Help
  • Live Chat
  • Contact
  • Email to our Support Team