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Biomarkers - Articles and news items
Issue 2 2008, Past issues / 19 March 2008 /
The impact of biomarker technology and biomarker strategies in pharmaceutical development is still in its infancy; but the impact is already proving significant. Biomarker strategy forms the basis for personalised medicine, the industry/regulatory focus centres on improving the success rate and reducing the high attrition rate often encountered in early phases of clinical research. The depth and breadth of knowledge required to successfully implement biomarkers into drug development is generating company collaborations and inclusion of professionals that have not traditionally been part of drug product development.
Today, we are witnessing a revolution in the understanding of health and disease, spurred on by the sequencing of the human genome and the subsequent creation of a map of human genetic variation. This revolution has been given a name: personalised medicine. (more…)
Issue 3 2007 / 23 May 2007 / Professor Stephen R Pennington, Proteome Research Centre, Conway Institute of Biomolecular and Biomedical Sciences, University College Dublin
Until recently the use of proteomics in the biomedical arena has included programmes aimed at the elucidation of cellular responses to extracellular stimuli by known and potential drugs. It has been anticipated that these will lead to the elucidation of the basic mechanisms of cellular responses, potential identification of new drug targets and discovery of the mechanism of action of drugs both NCE’s and those currently in development.
In addition, the use of proteomics to investigate toxic responses to drugs (toxicoproteomics) in pre-clinical and clinical studies has gained increasing importance, particularly when such data is analysed in the context of more traditional toxic responses. Notably, many of these studies are now undertaken in the context of multi-team groups or a consortia of researchers from different disciplines – including proteomics. An interesting example of such a consortium is the EU and commercially funded ‘PredTox’ predictive toxicology programme being undertaken by a range of companies and Universities; the programme forms part of the ‘Innovative Medicines for Europe’ initiative. There are important lessons to be learnt from the operational management of such consortia (to be discussed further on within the article). The PredTox programme is exemplary of the growing interest in the use of ‘omics technologies, including proteomics, to identify ‘biomarkers’, as well as a vibrant debate on the relative importance of biomarkers for revenue generation in the pharma sector. Here, the term ‘biomarkers’ will be defined in the context of proteomics, an historical overview of the evolution of proteomics technologies and their continuing development will be given, and some recent biomarker discovery projects will be outlined with the use of selected examples. To conclude, some of the lessons learnt and challenges that remain in biomarker discovery, validation and implementation will be summarised. (more…)
Issue 2 2007, Past issues / 27 March 2007 / Claudio Carini, MD,PhD,FRCPath, F. VP of Translational Medicine, MDS Pharma
Biomarkers are useful characteristics to evaluate disease progress and targets of therapeutic agents. They are objectively measured and obtained by non-invasive procedures collecting readily accessible matrixes (Blood, CSF). Biomarkers should be easy to detect, specific and reproducible. Most importantly when detected early in the course of a disease they should be effective in predicating long term clinical response.
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Issue 6 2006, Past issues / 28 November 2006 / Irina Antonijevic, Douglas Craig and Christophe Gerald, Lundbeck Research USA, Inc.
Only a few innovations have been made in recent decades with regard to psychiatric, and particularly antidepressant, drugs (Insel et al., 2006) (Figure 1). This conundrum reflects, at least partly, the lack of understanding of the disease biology. This poses a challenge not only to inventive drug development, but also to clinical practice, which faces remission rates of 30 per cent and less in patients given state-of-the-art pharmacological treatment for major depressive disorders (Trivedi et al., 2006). The situation is further aggravated by the exclusive current use of clinically based diagnostic criteria for major depression, which some critics view as ‘a pseudo-category, effectively homogenizing multiple expressions of depression’ (Parker, 2004).
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Issue 3 2005, Past issues / 22 August 2005 / Dr Graham R Betton, Senior Principal Scientist, Safety Assessment, AstraZeneca Pharmaceuticals
This article reviews the types of biomarkers currently available and approaches to discovering new biomarkers.
The category of type 0 biomarkers refers to pre-existing factors that influence disease susceptibility, outcome or therapeutic response (efficacy or toxicity) (Downing 2000). These markers may be genetic or acquired during life (e.g. viral infection, mutations in cancer) and constitute risk factors for disease. They equally form the basis of animal disease models, e.g. Zucker diabetic rats. The completion of the human genome and ongoing identification of the genetic polymorphisms and mutations within the germ line and cancer tissues has confirmed the previously unidentified existence of many patient subsets (Bertucci 2003). Consequently target selection for drug discovery has become more complex and the diagnostic challenges of personalised medicine and acquisition of human tissue banks from ethical and consented sources, compliant with the UK Human Tissue Act 2004, are now a priority for drug discovery. Personalised medicine is also a challenge for the commercial viability of niche new medical entities (NMEs) (Ross 2003, Lesko 2004). If clinical trial recruitment can be selectively based on patient subsets expressing the drug target, a better efficacy response could be anticipated, increasing the power of the clinical trial and attaining evidence for efficacy more rapidly as less patients need to be recruited. However smaller trials may impair the safety profiling of an NME. The technical means of screening hundreds of patient disease material samples (biofluids or tissue biopsies) is highly dependant on reagents (in particular antibodies) and tissue samples with reliable quality and provenance. The creation of tissue microarrays (TMAs) of clinical diagnostic biopsies and immunohistochemical staining for target protein expression allows for both the overall (brown) intensity of expression and heterogeneity of expression (e.g. cancer cell versus stroma, see Figure 1) and can enable early selection of target patient populations and individual cases.
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Issue 2 2005, Past issues / 20 May 2005 / William Carley, Ph.D., Experimental Medicine, Pfizer Global R&D
Biomarker application during drug development is driven by the need to define disease and therapeutic efficacy/safety earlier, better and with reduced cost.
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Issue 1 2005, Past issues / 7 March 2005 / Thorir D. Bjornsson, MD, PhD, Translational Development, Wyeth Research
The past decade has witnessed a growing interest in biomarkers, previously referred to as pharmacodynamic markers, PD markers, or pharmacologic read-outs. This increasing interest has been largely driven by evolutionary changes in drug discovery and development and in regulatory science1,2,3. One key driver has involved the increasing need to reach early go/no-go decisions about an increasing number of compounds entering early clinical development each year.
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