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Updated: Jan 29, 2026
Testing Targeted Therapies in Cancer using Structural DNA Alteration Analysis and Patient-Derived Xenografts
Published on: July 25, 2020
Tumor Tissue Explant Culture of Patient-Derived Xenograft as Potential Prioritization Tool for Targeted Therapy
Susmita Ghosh1, Manu Prasad1, Kiran Kundu1,2
1The Shraga Segal Department of Microbiology, Immunology and Genetics, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer Sheva, Israel.
Abstract:
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 2 × 2 × 2 mm3 explants and treated with clinically relevant drugs for 24 h. 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 h to be the time frame to detect drug responses and drug penetrates 2 × 2 × 2 mm3 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 efficient 3D 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.
Insights
A new tumor ex vivo analysis (TEVA) system accurately predicts head and neck cancer patient drug responses. This 3D tissue method bypasses lengthy animal studies, offering a faster, cost-effective preclinical drug screening approach.
Area of Science:
- Oncology
- Translational Research
- Preclinical Drug Development
Background:
- Head and neck cancer (HNC) survival rates remain low despite therapeutic advancements.
- Predicting patient-specific responses to HNC therapy is challenging, highlighting the need for effective preclinical models.
- Current preclinical models often lack the predictive accuracy for clinical drug response.
Purpose of the Study:
- To develop and validate an accurate, time-efficient tumor ex vivo analysis (TEVA) system for predicting patient-specific drug responses in HNC.
- To establish a correlation between ex vivo drug efficacy in TEVA and in vivo efficacy in patient-derived xenografts (PDXs).
- To provide a robust preclinical model that bypasses the need for extensive animal testing.
Main Methods:
- Generation and utilization of six patient-derived xenografts (PDXs) for TEVA.
- Preparation of 2x2x2 mm³ PDX explants and treatment with clinically relevant drugs for 24 hours.
- Evaluation of tumor cell proliferation and death via immunohistochemistry, calculation of TEVA scores, and comparison with in vivo PDX drug efficacy studies.
Main Results:
- TEVA demonstrated that 24 hours is sufficient to detect drug responses and observe drug penetration within explants, evidenced by altered signaling pathways.
- Tumor responses observed in the TEVA system significantly correlated with drug efficacy in vivo studies using PDXs.
- The study validated the efficacy of both single-agent and combination drug therapies within the TEVA system.
Conclusions:
- The developed TEVA system is a low-cost, robust, and efficient 3D tissue-based method for predicting HNC patient response to targeted and chemotherapies.
- TEVA offers a viable alternative to traditional drug validation in PDX-bearing mice, accelerating preclinical drug screening.
- This method holds potential for guiding personalized treatment strategies in head and neck cancer.
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