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SDIRSACR Oncology Insights

multiple therapies. These findings underscore the need for advanced 3D models and support targeting ALT, XIAP, DHFR,
and cytoskeletal regulators in future treatment strategies.

References:

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Acknowledgments and funding: This work was supported by the Croatian Science Foundation (HRZZ) under Grant No.
IP-2019-04-1157, IP-2018-01-7590 and DOK-2021-02-7662. The authors gratefully acknowledge the support received
through the 10x Genomics–Labena Challenge, which enabled single-cell transcriptomic profiling. We also thank the
Althium team for providing access to and support with HoloMonitor imaging, and the CellDynamics team for their
expertise in biophysical assessment and data analysis of spheroids using the W8 device.

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Bridging the Gap: The Role of PDTX Models in Cancer Therapy Development

Ivan Ranđelović , Mihály Cserepes 1, Attila Kigyós , József Tóvári 1
1
2
1Department of Experimental Pharmacology and the National Tumor Biology Laboratory, National Institute of Oncology,
Budapest, Hungary
2KINETO Lab Ltd., Budapest, Hungary

Keywords: animal experimentation, disease models animal, drug development, drug evaluation

Background: The continuous need for more effective anticancer therapies has driven the production of a vast number
of drug candidates. These compounds are typically subjected to rigorous preclinical testing, often relying on traditional
rodent xenograft models. While these models provide useful pharmacokinetic data, their reliance on cell line-derived
xenografts (CDX) poses significant limitations. CDX models lack the cellular and genetic diversity as well as the spatial
characteristics of patient tumors, leading to discrepancies between preclinical outcomes and clinical efficacy [1]. As
a result, many promising drug candidates fail in clinical trials, with a reported attrition rate of approximately 95%.
The majority of these failures stem from a lack of efficacy which is issue that could potentially be identified earlier
with more predictive models. In this context, Patient-Derived Tumor Xenograft (PDTX) models offer a transformative
approach to cancer drug development.PDTX models are established by directly implanting patient tumor tissue into
immunodeficient mice, thereby preserving the original tumor’s architecture, heterogeneity, and microenvironment
[2]. Unlike CDX models or conventional 2D cultures, PDTXs better mimic human tumor behavior and response to
therapy, providing a clinically more relevant platform for drug screening.With the field of oncology increasingly
oriented towards precision medicine, the role of PDTX models is gaining prominence. They help reduce clinical trial
failures, streamline drug development timelines, and lower associated costs. By bridging the translational gap between
preclinic and clinic studies, PDTX models represent a vital step towards more effective and individualized cancer
treatments. Patient-Derived Tumor Xenograft (PDTX) models have become a cornerstone in translational oncology,
accurately modeling human cancers and more realistic drug response patterns. Unlike conventional cell line-based
models, PDTXs preserve the essential biological features of the original clinical tumors, making them uniquely suited
for preclinical drug development and personalized therapy approaches.PDTX models preserve key properties of clinical

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