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.
Highlights
Despite recognition of the condition for many centuries [1], intense research efforts and generous funding, cancer remains a major threat to mortality and morbidity globally [2]
‘Clinical Trial’ filter to see how many of the published papers were associated with clinical trials, and we used the National Institutes of Health (NIH) RePORT database to further search for clinical trials that are using organoids or xenografts
We collated the available data on projects funded by the NIH and through the European framework programs to estimate the prevalence of Patient-derived xenograft (PDX) versus patient-derived organoids (PDO) in research projects
Summary
Despite recognition of the condition for many centuries [1], intense research efforts and generous funding, cancer remains a major threat to mortality and morbidity globally [2]. According to the Globocan database (details in Table 1), the five types of cancer with the highest mortality (deaths recorded in 2018) are as follows: lung (1,761,007), colorectal (880,972), stomach (782,685), liver (781,631) and breast (626,679). Whilst there are regional differences in incidence and mortality, Europe, the UK and the US follow this global trend, with lung, breast, and colorectal cancers accounting for the top three cancer-related mortalities. The Community Research and Development Information Service (CORDIS) is the European Commission’s primary source of results from the projects funded by the EU’s framework programmes for research and innovation (FP1 to Horizon 2020).
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