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Original Research ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Oncol. | doi: 10.3389/fonc.2019.00017

Tumor Tissue Explant Culture of Patient-Derived Xenograft as Potential Prioritization Tool for Targeted Therapy

 Susmita Ghosh1, Manu Prasad1,  Kiran Kundu1, Limor Cohen1, Ksenia Yegodayev1, Jonathan Zorea1, Joshua Ben-zion1, 2, Batel Lasry1, 2, Orr Dimitstein1, 2, Anat Bahat-Dinur1, 2,  Aviram Mizrachi3, 4, Vladimir Lazar5,  Moshe Elkabets1* and  Angel Porgador1*
  • 1Ben-Gurion University of the Negev, Israel
  • 2Soroka Medical Center, Israel
  • 3Rabin Medical Center, Israel
  • 4Tel Aviv University, Israel
  • 5Worldwide Innovative Network (WIN) Association - WIN Consortium, France

Despite of remarkable progress made in the head and neck cancer (HNC) therapy, the survival rate of this metastatic disease remain low. Tailoring the appropriate therapy to patients is a major challenge and highlights the unmet need to have a good preclinical model that will predict clinical response. Hence, we developed an accurate and time efficient drug screening method of tumor ex vivo analysis (TEVA) system, which can predict patient-specific drug responses. In this study, we generated six patient derived xenografts (PDXs) which were utilized for TEVA. Briefly, PDXs were cut into 2x2x2mm3 explants and treated with clinically relevant drugs for 24 hours. Tumor cell proliferation and death were evaluated by immunohistochemistry and TEVA score was calculated. Ex vivo and in vivo drug efficacy studies were performed on four PDXs and three drugs side-by-side to explore correlation between TEVA and PDX treatment in vivo. Efficacy of drug combinations was also ventured. Optimization of the culture timings dictated 24 hours to be the time frame to detect drug responses and drug penetrates 2x2x2mm3 explants as signaling pathways were significantly altered. Tumor responses to drugs in TEVA, significantly corresponds with the drug efficacy in mice. Overall, this low cost, robust, relatively simple and efficient3D tissue-based method, employing material from one PDX, can bypass the necessity of drug validation in immune-incompetent PDX-bearing mice. Our data provides a potential rationale for utilizing TEVA to predict tumor response to targeted and chemo therapies when multiple targets are proposed.

Keywords: head and neck cancer, patient derived xenografts (PDX), ex vivo, Explant culture, targeted therapy

Received: 18 Oct 2018; Accepted: 07 Jan 2019.

Edited by:

Giovanna Schiavoni, Istituto Superiore di Sanità (ISS), Italy

Reviewed by:

Silviya P. Zustiak, Saint Louis University, United States
Natalie J. Serkova, School of Medicine, University of Colorado, United States  

Copyright: © 2019 Ghosh, Prasad, Kundu, Cohen, Yegodayev, Zorea, Ben-zion, Lasry, Dimitstein, Bahat-Dinur, Mizrachi, Lazar, Elkabets and Porgador. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence:
Dr. Moshe Elkabets, Ben-Gurion University of the Negev, Beersheba, Israel, moshee@post.bgu.ac.il
Prof. Angel Porgador, Ben-Gurion University of the Negev, Beersheba, Israel, angel@bgu.ac.il