Alzheimer’s Disease, and Breast and Prostate Cancer Research: Translational Failures and the Importance to Monitor Outputs and Impact of Funded Research

Herrmann, Kathrin; Bernasconi, Camilla; McCarthy, Janine; Campia, Ivana; Desaintes, Christian; Wittwehr, Clemens; Deceuninck, Pierre; Whelan, Maurice

doi:10.3390/ani10071194

Cited by 18 publications

(16 citation statements)

References 148 publications

(201 reference statements)

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“…Whilst our conclusions are necessarily limited, and we cannot accurately calculate the proportion of funding allocated to projects dedicated to the newer, human-relevant technologies as total replacement for animals, we did see that, for NIH projects funded in 2019 alone, R01 research projects using mouse xenograft models for breast cancer research attracted over five times greater support than projects using organoids to explore breast cancer ( Table 3 ). It is concerning that research projects using animal models continue to attract substantially more funding than human-based methods, and that this sustained reliance on animal models is associated with a less-than-optimal return on investment [ 20 ]. We suggest that funding calls specifically encourage or require the use of human-specific non-animal technologies for human disease research and no longer accept or request funding applications that require the use of animal models.…”

Section: Discussionmentioning

confidence: 99%

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

Marshall

Triunfol

Seidle

2020

Animals

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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

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Section: Discussionmentioning

confidence: 99%

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

Marshall

Triunfol

Seidle

2020

Animals

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“…Organoids foster the establishment of improved, “real” disease models for experimental research [ 135 ]. Cerebral organoids, also known as mini brains, can be generated from patients suffering from Alzheimer’s or Parkinson’s disease [ 136 , 137 ], pancreatic organoids from diabetes patients [ 138 ], intestinal organoids from people suffering from inflammatory bowel diseases [ 139 ], and 3D lung models from smokers, COPD (chronic obstructive pulmonary disease) or asthma patients [ 140 ]. These models offer numerous applications and have boosted biomedical research in recent years.…”

Section: Human Intestinal Organoids and How They Can Improve Drug Screeningmentioning

confidence: 99%

Drug Screening, Oral Bioavailability and Regulatory Aspects: A Need for Human Organoids

Zietek

Boomgaarden²,

Rath

2021

Pharmaceutics

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The intestinal epithelium critically contributes to oral bioavailability of drugs by constituting an important site for drug absorption and metabolism. In particular, intestinal epithelial cells (IEC) actively serve as gatekeepers of drug and nutrient availability. IECs’ transport processes and metabolism are interrelated to the whole-body metabolic state and represent potential points of origin as well as therapeutic targets for a variety of diseases. Human intestinal organoids represent a superior model of the intestinal epithelium, overcoming limitations of currently used in vitro models. Caco2 cells or rodent explant models face drawbacks such as their cancer and non-human origin, respectively, but are commonly used to study intestinal nutrient absorption, enterocyte metabolism and oral drug bioavailability, despite poorly correlative data. In contrast, intestinal organoids allow investigating distinct aspects of bioavailability including spatial resolution of transport, inter-individual differences and high-throughput screenings. As several countries have already developed strategic roadmaps to phase out animal experiments for regulatory purposes, intestinal organoid culture and organ-on-a-chip technology in combination with in silico approaches are roads to go in the preclinical and regulatory setup and will aid implementing the 3Rs (reduction, refinement and replacement) principle in basic science.

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“…On the other hand, the expanding toolbox of non-animal methods — such as induced pluripotent stem cells derived from patients, next-generation sequencing, ‘omics’ and integrated computer modelling — can be used to study human diseases in human-based settings, identify new potential druggable targets and evaluate treatment effects. 7,8 The rise of new technological tools and models in life science, and the increasing need for multidisciplinary approaches, have encouraged many research initiatives and the launch of new EU calls for proposals. Research proposals based on the use of both animal and/or non-animal approaches have been extensively funded at European level.…”

Section: Speakers At the 2021 Jrc Summer Schoolmentioning

confidence: 99%

“…Nowadays, it is becoming pivotal to define and apply indicators suitable to measure the social impact of research funding strategies, monitor contribution to innovation, retrospectively assess public health trends, and readdress funding strategies when needed. 8 Here we discuss such issues, describing a list of indicators to measure the impact and innovation of biomedical research.…”

Section: Speakers At the 2021 Jrc Summer Schoolmentioning

confidence: 99%

JRC Summer School on Non-animal Approaches in Science, May 2021

Landesmann

Paini

2021

Altern Lab Anim

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Background"The JRC Summer School on Non-animal Approaches in Sciencea flair of holidays and fun. Learning and socialising, intellectual challenge and playful competition." That was our tempting vision, back in 2016, for installing such a training course at EURL ECVAMand we decided to go for it. We already had some experience in this respect, as every year students from the Karolinska Toxicology Master course programme visited the EURL ECVAM laboratories to learn more about non-animal methods and regulatory toxicology, and to have a closer look on the life in an international research centre such as the Joint Research Centre (JRC).Our aim was to share knowledge and experience on the latest non-animal approaches in science with young scientists and professionals, to give them new insights and to enable networking and exchange among all participantsstudents as well as invited experts and ourselves at the JRC. We wanted the experience to be as interactive as possible for the students, hopefully eliciting input from every participant.With the approval of our hierarchy, a rather small group of brave people started to tackle the preparatory work for the inaugural summer school, which turned out to be quite extensive. Besides the elaboration of the programme itself, there was also a broad range of logistical challenges. Increasingly more people became involved, beyond the staff of our unitfor example, technical, catering, cleaning, transport and security services were all required. Many people had to be transported around (local public transport is, to put it mildly, suboptimal), accommodated and fed. In order to reach as many students as possible to inform them about the event, a range of different communication channels were explored. To limit the participation to our targeted audience, i.e. students or early-career scientists (maximum of four years post-masters or PhD) in relevant fields, and to ensure a good level of existing scientific education, we asked for a motivation letter, a CV and a poster abstract to be submitted along with the application. Based on these pre-defined criteria, these documents were used for the selection of participants.

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Alzheimer’s Disease, and Breast and Prostate Cancer Research: Translational Failures and the Importance to Monitor Outputs and Impact of Funded Research

Cited by 18 publications

References 148 publications

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

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

Drug Screening, Oral Bioavailability and Regulatory Aspects: A Need for Human Organoids

JRC Summer School on Non-animal Approaches in Science, May 2021

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