Patient-Derived Xenograft vs. Organoids: A Preliminary Analysis of Cancer Research Output, Funding and Human Health Impact in 2014–2019

Abstract

Cancer remains a major threat to mortality and morbidity globally, despite intense research and generous funding. Patient-derived xenograft (PDX) models—where tumor biopsies are injected into an animal—were developed to improve the predictive capacity of preclinical animal models. However, recent observations have called into question the clinical relevance, and therefore the translational accuracy, of these. Patient-derived organoids (PDO) use patient tumor samples to create in vitro models that maintain aspects of tumor structure and heterogeneity. We undertook a preliminary analysis of the number of breast, colorectal, and lung cancer research studies using PDX or PDO published worldwide between 2014–2019. We looked for evidence of impacts of this research on human health. The number of publications that focused on PDO is gradually increasing over time, but is still very low compared to publications using PDX models. Support for new research projects using PDO is gradually increasing, a promising indicator of a shift towards more human-relevant approaches to understanding human disease. Overall, increases in total funding for these three major cancer types does not appear to be translating to any consequential increase in outputs, defined for this purpose as publications associated with clinical trials. With increasing public discomfort in research using animals and demands for ‘alternative’ methods, it is timely to consider how to implement non-animal methods more effectively

Organoids and Colorectal Cancer

“…Compared to PDX, PDTOs save animal testing, have a lower cost:benefit ratio, require less specialized facilities, can be stored as living biobanks, and are more amenable to drug screening [ 96 , 97 ] ( Table 2 ). Organoids are therefore a suitable complement to tumor genome sequencing and xenograft studies for predicting patient responses to treatments and could in the future be responsible for the reduction of animal testing in biomedical research [ 2 , 98 , 99 , 100 , 101 ].…”

Breast Cancer Organoids Model Patient-Specific Response to Drug Treatment

“…Major advantages of these models are represented by the possibility to study the response to drug treatments in vivo, as well as to model metastasis and, to some extent, the TME. However, the use of immunocompromised mice prevents investigating the contribution of the immune system, which is a major limitation of these models [ 7 ]. Moreover, maintenance of PDX is time-consuming, expensive, and not suitable for high-throughput screenings.…”

“…Moreover, maintenance of PDX is time-consuming, expensive, and not suitable for high-throughput screenings. Many of these limitations can be overtaken by the generation of patient-derived tumor organoids (PDOs) [ 7 ]. These are tumor cells-derived three-dimensional (3D) cultures generated from cancer biopsies, cultivated in ECM surrogates with specific niche factors.…”

Effect of the Marine Polyketide Plocabulin on Tumor Progression

“…The xenograft model is an excellent experimental approach for predicting drug response in human tumors [ 28 ]. The anticancer effects of plocabulin were reported in six subcutaneous human-derived xenografted tumors (MDA-MB-231, HCT-116, HGC-27, H-460, 22RV1 and Caki-1) in female athymic nu/nu mice models.…”