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.

Keywords: breast cancer; colorectal cancer; lung cancer; patient-derived organoids; patient-derived xenografts; research outputs.

Figure 1

Publications for each type of cancer investigated, and associations with clinical trials. Panel A shows the total number of published studies retrieved from PubMed during the period 2014–2019, for each type of cancer, regardless of the technology used. For each of the three cancer types, the number of publications is reduced over time. Panel B shows that the same was true for studies associated with clinical trials, where the number of published studies associated with a clinical trial decreased for each cancer type between 2014 to 2019.

Figure 2

Publications employing patient-derived xenograft (PDX) or patient-derived organoids (PDO) for each cancer type, and their association with clinical trials. The proportion of papers published between 2014–2019 for breast, lung and colorectal cancers using PDX or PDO, relative to the total number of papers published for each cancer type, regardless of the technology used, and the papers associated with a clinical trial are shown. Blue bars indicate the proportion of papers using each technology, relative to the total number of papers for that specific cancer type, and orange bars indicate the proportion of papers associated with a clinical trial. Data were retrieved from PubMed as described in the Methods.

Figure 3

Year-on-year analysis of the number of papers published worldwide using PDX (A), the proportion of those papers that used PDX and were associated with clinical trials (B), and the number of papers published using PDO (C). The number of studies using PDX, for all three types of cancer, shows some fluctuations but overall remain the same over the time period evaluated (A). Likewise, there is no growing trend for the number of publications using PDX and associated with clinical trials between 2014 and 2019 (B)—these data are expressed as the number of studies associated with a clinical trial relative to the total number of publications using PDX. However, panel C shows that the number of published studies using PDO increase over time but note that the total number of papers is still low compared to the number of studies using PDX (panel A).

Figure 4

Research using PDX or PDO that declared an affiliation to the US. Panel A: The number of studies using PDX during the 2014-2019 period showed some fluctuations but overall remained the same during the period. Panel B shows the number of studies using PDX during the period 2014–2019 that received National Institutes of Health (NIH) funding. Note that the number of studies has not increased over the years. Panel C: The proportion of studies using PDX, relative to the total number of using PDX, which were associated with clinical trials, does not show a growing trend. Panel D indicates that research using PDO is on the increase in the US. Panel E shows the number of studies using PDO that received funds from NIH and indicates that most studies using PDO in the US are NIH-funded (or part NIH-funded).

Figure 5

Funding for cancer research in the UK (panels A and C) and US (panels B and D) between 2014 and 2019. Data were retrieved from National Cancer Research Institute (NCRI) and NIH databases for the UK and US, respectively. Panels A and B show funding for each selected cancer type for the UK and US, respectively, revealing relatively generous support for breast cancer for both regions. Panels C and D are the funding for the selected cancer types relative to total cancer funding, for the UK and US, respectively. Support has been sustained or increased slightly over time for both regions.