EU Framework 6 Project: Predictive Toxicology (PredTox)—overview and outcome

Suter, Laura; Schroeder, Susanne; Meyer, Kirstin; Gautier, Jean‐Charles; Amberg, Alexander; Wendt, Maria; Gmuender, Hans; Mally, Angela; Boitier, Eric; Ellinger‐Ziegelbauer, Heidrun; Matheis, Katja; Pfannkuch, F

doi:10.1016/j.taap.2010.10.008

Cited by 68 publications

(33 citation statements)

References 21 publications

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“…Several large TGx databases derived from well-designed studies are available such as The Open Japanese Toxicogenomics Project (TG-GATEs) (Uehara et al, 2010;Igarashi et al, 2015), DrugMatrix (Ganter et al, 2005) and PredTox (Suter et al, 2011). These databases provide the opportunity to evaluate systematically different TGx assay probe-level data of the microarrays were quantile normalized.…”

Section: Microarray Data Processingmentioning

confidence: 99%

In vitro to in vivo extrapolation for drug-induced liver injury using a pair ranking method_suppl

Liu¹

2017

ALTEX

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Section: Microarray Data Processingmentioning

confidence: 99%

In vitro to in vivo extrapolation for drug-induced liver injury using a pair ranking method_suppl

Liu¹

2017

ALTEX

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“…49 When ''omics'' are used either alone or better yet in conjunction with other technologies (systems biology approach), they can rapidly fill the gap in the development of new minimally invasive and easily accessible biomarkers in preclinical and clinical studies. 24,48,85 Systems biology is the combination of the ''omics'' platforms, bioinformatics, and other biologic data, which focuses on interactions within and between the mechanisms that combine to give rise to the function and behavior of a biological system. 34,89 Deciphering complex, highly networked, and pleiotropic pathways that give rise to adverse events aids in the identification of specific biomarkers, which ultimately helps us understand the patient risks and improves the overall safety testing process.…”

Section: Transcriptomics Metabonomics/metabolomics and Proteomicsmentioning

confidence: 99%

Safety Biomarkers in Preclinical Development

Sasseville¹,

Mansfield²,

Brees

2013

Vet Pathol

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The identification, application, and qualification of safety biomarkers are becoming increasingly critical to successful drug discovery and development as companies are striving to develop drugs for difficult targets and for novel disease indications in a risk-adverse environment. Translational safety biomarkers that are minimally invasive and monitor drug-induced toxicity during human clinical trials are urgently needed to assess whether toxicities observed in preclinical toxicology studies are relevant to humans at therapeutic doses. The interpretation of data during the biomarker qualification phase should include careful consideration of the analytic method used, the biology, pharmacokinetic and pharmacodynamic properties of the biomarker, and the pathophysiology of the process studied. The purpose of this review is to summarize commonly employed technologies in the development of fluidand tissue-based safety biomarkers in drug discovery and development and to highlight areas of ongoing novel assay development.

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“…The evolving concept of systems biology is starting to be adopted by the pharmaceutical industry and integrated into the safety sciences. A recent example of a substantial move forward in this field is the European Union Framework 6 Project on Predictive Toxicology, which compared conventional toxicologic endpoints for several investigational compounds to transcriptomics, proteomics, and metabolomics profiles (27). These researchers found that the use of systems biology was instrumental in determining mechanisms of nephrotoxicity and hepatotoxicity as well as identifying potential predictive biomarkers.…”

Section: A Pathway Forwardmentioning

confidence: 99%

Identification and Elucidation of the Biology of Adverse Events: The Challenges of Safety Assessment and Translational Medicine

Turteltaub

Davis

Burns‐Naas

et al. 2011

Clinical Cancer Research

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There has been an explosion of technology-enabled scientific insight into the basic biology of the causes of adverse events. This has been driven, in part, by the development of the various "omics" tools (e.g., genomics, proteomics, and metabolomics) and associated bioinformatics platforms. Meanwhile, for decades, changes in preclinical testing protocols and guidelines have been limited. Preclinical safety testing currently relies heavily on the use of outdated animal models. Application of systems biology methods to evaluation of toxicities in oncology treatments can accelerate the introduction of safe, effective drugs. Systems biology adds insights regarding the causes and mechanisms of adverse effects, provides important and actionable information to help understand the risks and benefits to humans, focuses testing on methods that add value to the safety testing process, and leads to modifications of chemical entities to reduce liabilities during development. Leveraging emerging technologies, such as genomics and proteomics, may make preclinical safety testing more efficient and accurate and lead to better safety decisions. The development of a U.S. Food and Drug Administration guidance document on the use of systems biology in clinical testing would greatly benefit the development of drugs for oncology by communicating the potential application of specific methodologies, providing a framework for qualification and application of systems biology outcomes, and providing insight into the challenges and limitations of systems biology in the regulatory decision-making process. Clin Cancer Res; 17(21); 6641-5. Ó2011 AACR. Introductory NoteAt the 2010 Conference on Clinical Cancer Research, co-convened by Friends of Cancer Research and the Engelberg Center for Health Care Reform at the Brookings Institution, participants explored 4 pressing new challenges in the field. Articles summarizing the panel's recommendations on each of these topics are featured in this issue of Clinical Cancer Research (1-4). Gaps in Current Testing and Safety Assessment ParadigmsThe toxicity of new oncology drugs is a leading cause of pharmaceutical attrition and a major impediment to efficient and successful drug development. Safety, or lack thereof, is also a major factor in regulatory decisions involving drug approval, labeling, risk evaluation, and mitigation and even withdrawal from the marketplace. The current battery of preclinical safety studies required to support the clinical development of new drugs and marketing approval is mapped out in International Conference on Harmonisation (ICH) guidelines that include ICH M3, E14, and S1 to S9 (5). In addition, various other documents from regulatory agencies provide recommendations regarding specific toxicities or adverse events, such as hepatotoxicity (6). However, these testing methods and risk assessments have not kept pace with the rapid evolution of technology, biomedical research, and knowledge generation. For example, the studies required to meet international regulatory...

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EU Framework 6 Project: Predictive Toxicology (PredTox)—overview and outcome

Cited by 68 publications

References 21 publications

In vitro to in vivo extrapolation for drug-induced liver injury using a pair ranking method_suppl

In vitro to in vivo extrapolation for drug-induced liver injury using a pair ranking method_suppl

Safety Biomarkers in Preclinical Development

Identification and Elucidation of the Biology of Adverse Events: The Challenges of Safety Assessment and Translational Medicine

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