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The Use of Endometrial Cancer Patient–Derived Organoid Culture for Drug Sensitivity Testing Is Feasible
  1. Eugenia Girda, MD*,
  2. Eric C. Huang, MD, PhD,
  3. Gary S. Leiserowitz, MD* and
  4. Lloyd H. Smith, MD, PhD*
  1. *Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, and
  2. Department of Pathology and Laboratory Medicine, UC Davis Comprehensive Cancer Center, UC Davis Medical Center, Sacramento, CA.
  1. Address correspondence and reprint requests to Eugenia Girda, MD, Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, UC Davis Medical Center, 4860 Y St, Suite 2500, Sacramento, CA 95817. E-mail: egirda@ucdavis.edu.

Abstract

Objective Patient-derived organoids (PDOs), used in multiple tumor types, have allowed evaluation of tumor characteristics from individual patients. This study aimed to assess the feasibility of applying PDO in vitro culture for endocrine-based and drug sensitivity testing in endometrial cancer.

Methods Endometrial cancer cells were enzymatically dissociated from tumors retrieved from fresh hysterectomy specimens and cultured within basement membrane extract in serum-free medium. An organoid growth assay was developed to assess the inhibitory effects of a variety of drugs including endocrine treatments. Organoid cultures were also prepared for histological and immunohistochemical comparison to the tumors of origin.

Results Fifteen endometrial cancer specimens were successfully cultured as PDOs. Small spherical structures formed within 24 hours, and many continued to grow to larger, denser organoids, providing the basis for an organoid growth assay. The STAT3 transcription factor inhibitor, BBI608 (Napabucasin), strongly inhibited growth in almost all PDO cultures, suggesting that stemness programing is involved in organoid formation and/or growth. Inhibition by different growth factor receptor tyrosine kinase inhibitors was observed in several PDO specimens. Four cultures were inhibited by fulvestrant, implying the importance of estrogen-receptor signaling in some PDO cultures. Organoids closely resembled their tumors of origin in both histomorphology and immunohistochemical expression.

Conclusions The use of endometrial cancer PDO cultures for development of drug sensitivity testing for individual patient tumors is feasible. The potential value of the PDO model for clinical decision making will require clinical trial evaluation.

  • Endometrial cancer
  • Patient-derived organoids (PDOs)
  • Stemness

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Footnotes

  • Support was provided through research funds from the Department of Obstetrics and Gynecology at UC Davis.

  • The authors declare no conflicts of interest.

  • Supplemental digital content is available for this article. Direct URL citation appears in the printed text and is provided in the HTML and PDF versions of this article on the journal’s Web site (www.ijgc.net).

  • This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.

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