Importance of Patient-Derived Xenograft Models in Battling Cancer Therapy Resistance

Cancer accounts for approximately ten million deaths annually. The majority of these are attributable to resistance-driven tumor progression and metastasis. Although increasingly effective, precise, and selective therapeutic strategies are being developed, cancer cells retain the capacity to dynamically alter their phenotype and evade treatment. Traditional in vitro approaches rely heavily on cell line monocultures; however, their limited clinical translatability has driven the development of more advanced model systems. Three-dimensional in vitro models, including spheroids, organoids, and bioprinted tissues, provide more physiologically relevant and rapid insights, but fail to capture systemic pharmacodynamics and anatomical complexity. Emerging in vivo models, such as genetically engineered mouse models (GEMMs) of carcinogenesis and patient-derived xenografts (PDXs), as well as their derived organoids, provide a more comprehensive understanding of tumor biology. The preservation of tumor heterogeneity, microenvironment, and drug sensitivity profiles has positioned PDX models as widely used platforms in both drug development and therapy response prediction. Despite limitations-including variable engraftment rates, genetic drift, lack of fully functional immune systems, ethical concerns, and high costs-PDX models, when integrated with complementary techniques, contribute significantly to identifying novel therapeutic targets and combinations. Moreover, they support clinical decision-making by enabling drug response prediction based on genetic landscapes and co-clinical response data.