Impact of biomarker development on drug safety assessment

Marrer, Estelle; Dieterle, Frank

doi:10.1016/j.taap.2009.12.015

Cited by 83 publications

(46 citation statements)

References 68 publications

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“…Many drugs of our modern pharmacopeia are able to induce adverse effects that can involve different tissues such as the liver, heart, kidney, lung, skeletal muscles, adipose tissue, and peripheral nerves (Marrer and Dieterle 2010; Begriche et al. 2011; Hohenegger 2012; Tocchetti et al.…”

Section: Introductionmentioning

confidence: 99%

Role of endoplasmic reticulum stress in drug‐induced toxicity

Foufelle

Fromenty

2016

Pharmacology Res & Perspec

189

161

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Drug‐induced toxicity is a key issue for public health because some side effects can be severe and life‐threatening. These adverse effects can also be a major concern for the pharmaceutical companies since significant toxicity can lead to the interruption of clinical trials, or the withdrawal of the incriminated drugs from the market. Recent studies suggested that endoplasmic reticulum (ER) stress could be an important event involved in drug liability, in addition to other key mechanisms such as mitochondrial dysfunction and oxidative stress. Indeed, drug‐induced ER stress could lead to several deleterious effects within cells and tissues including accumulation of lipids, cell death, cytolysis, and inflammation. After recalling important information regarding drug‐induced adverse reactions and ER stress in diverse pathophysiological situations, this review summarizes the main data pertaining to drug‐induced ER stress and its potential involvement in different adverse effects. Drugs presented in this review are for instance acetaminophen (APAP), arsenic trioxide and other anticancer drugs, diclofenac, and different antiretroviral compounds. We also included data on tunicamycin (an antibiotic not used in human medicine because of its toxicity) and thapsigargin (a toxic compound of the Mediterranean plant Thapsia garganica) since both molecules are commonly used as prototypical toxins to induce ER stress in cellular and animal models.

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Section: Introductionmentioning

confidence: 99%

Role of endoplasmic reticulum stress in drug‐induced toxicity

Foufelle

Fromenty

2016

Pharmacology Res & Perspec

189

161

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“…TIMP-1 mRNA, and protein is upregulated in different models of renal disease and human sclerotic glomeruli there are still significant limitations, protein kidney dysfunction markers have been considered a door opening safety biomarker success story [273] and is a good example for how molecular marker tools for drug development can be expected to develop, be reviewed, and approved in the near future.…”

Section: -264mentioning

confidence: 99%

Proteo‐Metabolomic Strategies in the Future of Drug Development

Christians¹,

Schmitz²,

Klawitter³

et al. 2012

Analytical Techniques for Clinical Chemistry

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“…This case demonstrates how a systems biology approach can elucidate the pathophysiology of complex and dynamic biologic processes, create testable hypotheses related to these phenomena, and identify potential candidate biomarkers that can be assessed and validated as an indicator of the toxicity (15).…”

Section: Case Study 1: Drug-induced Vascular Injurymentioning

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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Impact of biomarker development on drug safety assessment

Cited by 83 publications

References 68 publications

Role of endoplasmic reticulum stress in drug‐induced toxicity

Role of endoplasmic reticulum stress in drug‐induced toxicity

Proteo‐Metabolomic Strategies in the Future of Drug Development

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

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