Biomarkers - Articles and news items

Whitepaper: Autoantibody biomarker panels for improved disease diagnosis

Whitepapers / 1 February 2012 / Oxford Gene Technology

New white paper discusses the advantages of autoantibody-based biomarkers

Download this free white paper for detailed insight into the advantages of autoantibodies as biomarkers, including a review of the current technology and best practices for identification of sensitive and specific autoantibody biomarkers.

Download the whitepaper to find out more:

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Discovery and validation of biomarkers for multiple sclerosis

Latest issue / 13 December 2011 / Ole Pless and Sheraz Gul, European ScreeningPort GmbH

Multiple Sclerosis (MS) is an autoimmune disease leading to a chronic inflammation and degeneration of the central nervous system. It is one of the major neurological diseases with approximately 2.5 million suffering patients worldwide. Until now, the underlying mechanisms have not been fully elucidated, but the cause of the disease can be modulated to limit progression and severity. Currently, there are no validated biomarkers available to predict the progression of MS or response to a clinical intervention apart from MRI. In order to identify protein biomarkers for MS as well as other diseases, significant infrastructure is required and this is discussed.

The term ‘biomarker’ has been defined as a “characteristic that is objectively measured and evaluated as an indicator of normal biological processes, pathogenic processes, or pharmacologic responses to a therapeutic intervention”1,2. The measurement of normal and dysfunctional biological processes and their changes in response to therapeutic intervention forms the basis of biomarkers. The advances in genetics and molecular biology leading to the sequencing of the human genome has resulted in the identification of a variety of novel targets implicated in different disease states3-5. Further technological developments including high throughput profiling of various samples using genomics, transcriptomics and proteomics6,7 has led to the identification of gene and protein based markers that characterise disease states for a number of indications including breast cancer8-10, colorectal cancer11 and cardiovascular diseases12. Additional initiatives that have led to the identification of biomarkers with minimal invasive methods such as proteomics technologies13 and systems biology14 have proven extremely effective for discovering potential biomarkers and drug targets. These technologies tend to provide large data sets that can be difficult to deconvolute for biomarker discovery. This bottleneck can be reduced by using several strategies. The first is to constrict the number of potential biomarkers and drug targets by dividing the proteome into smaller, more biologically significant segments. The second is to widen the bottleneck with higheroutput and higher-throughput screening technologies. The third is to incorporate more preliminary validation into the discovery process. New and emerging technologies provide promise for each of these strategies15. (more…)

Reverse phase protein microarrays for targeted analysis of cellular proteomes

Latest issue / 13 December 2011 / Ulrike Korf, DKFZ Heidelberg

In order to advance the identification of new drug targets and disease biomarkers, experimental tools for the systems-level analysis of signalling networks are required. Approaches for a targeted analysis of cellular proteomes have improved in recent years. Notably, the reverse phase protein microarray (RPPA) approach offers great advantages due to properties such as high sensitivity and high sample capacity. This review gives an overview of the principle of RPPA and summarises successful applications that illustrate the potential of RPPA for the analysis of clinical samples, systems biology and for drug discovery concepts. Numerous reports demonstrated the power of this approach to produce higher-order information than is currently possible with any other approach while requiring only minute amounts of sample.

Up-to-date, acquired experience on the application of targeted therapeutics revealed that patients benefit from drugs targeting molecules that are overexpressed by tumours. However, the percentage of patients truly benefiting from the targeted treatment depends largely on the type of tumour. In detail, clinical data obtained from the treatment of solid tumours suggests that our current knowledge is not sufficient to decide beforehand which patients will benefit from a certain treatment and which patients do not. This suggests that overexpression of a particular oncogenic protein by a tumour, such as EGFR, HER2, or oestrogen receptor, does not provide dependable information for treatment decisions. Considerable knowledge has been accumulated on the wiring of those pathways that convey information from cell surface receptors and neighbouring cells as well as the nutritional state and related physiological events. An obvious challenge for proteome research is to convert this knowledge into clinically and pharmaceutically relevant information. However, most drugs target proteins and therefore the realisation of personalised treatment concepts requires a systematic large-scale analysis of individual tumours to identify patterns of deregulation characteristic for subgroups of a certain type of cancer. The identification of reliable disease markers could then be translated into new treatment concepts which have been held back due to technological constraints. (more…)

Expression profiling of circulating miRNAs as a novel non-invasive diagnostic tool

Latest issue / 13 December 2011 / Mirco Castoldi. Department of Pediatric Hematology, Oncology and Immunology University of Heidelberg

Cell-free nucleic acids circulating in human blood were first described in 19481. However, it was not until the work of Sorengon and colleagues was published in 19942 that the importance of circulating nucleic acid (cfNA) was recognised. Today, the detection of diverse type of cfNA3 in blood and other body fluids is a valuable resource for the identification of a novel biomarker4,5. Although different types of cfNA have been described (including DNA, mRNA and microRNA), this review focuses on the isolation, detection and clinical utility of circulating microRNAs.

microRNAs (miRNAs) are an abundant class of short single stranded non-coding RNAs (~22 nts) that regulate gene expression at the posttranscriptional level. Interaction between an miRNA and any given of its mRNA targets results in either translation inhibition, mRNA degradation or a combination of both mechanisms. Therefore, miRNAs activity effectively reduces the transcriptional output of a target gene, without affecting its transcription rate. Currently, the sequence of over 60,000 microRNAs are deposited in the miRBase database [Version 17, April 20116]. miRNA activity has been associated with the control of a wide range of basic processes such as development, differentiation and metabolism. Detection of differential expression of miRNAs in many cases have established the basis for miRNA functional analysis and specific miRNA expression patterns can provide valuable diagnostic and prognostic indications, for example, in the context of human malignancies7,8. Moreover, the deregulation of the expression of miRNAs has been shown to contribute to cancer development through various kinds of mechanisms, including deletions, amplification or mutations involving miRNA loci, epigenetic silencing, as well as the dysregulation of transcription factors that target specific miRNAs9,10. (more…)

ICON selected by the Biomarkers Consortium of the FNIH

Industry news, News / 21 October 2011 / ICON plc

ICON has announced it has received a contract award from the Foundation for the National Institutes of Health (FNIH) to provide clinical support for the Biomarkers Consortium study entitled Characterization of the Variability of Insulin Secretory Parameters in the Meal Tolerance and the Maximal Stimulation Tests of Healthy Subjects. (more…)

HOX transcription factors as biomarkers in cancer

Issue 5 2011 / 19 October 2011 / Richard Morgan, Postgraduate Medical School, Faculty of Health and Medical Sciences, University of Surrey

The HOX genes are a family of closely related transcription factors that help to define the identity of cells and tissues during embryonic development and which are also frequently deregulated in cancer, where they have been shown to promote cell survival and proliferation. The high level of cancer-associated HOX expression and the pro-oncogenic functions of these genes make them strong candidates for biomarkers in multiple roles including diagnosis, prognosis, drug sensitivity and drug resistance.

The HOX genes are a family of homeodomaincontaining transcription factors that were first identified as determinates of cell and tissue identity in early development, although they are now also known to function in adult stem cell renewal and differentiation1. A series of duplication events is thought to have given rise to the four separate clusters of HOX genes found in vertebrates, with each cluster consisting of a group of closely linked members that often share enhancer regions. These clusters are named A, B, C and D, and together they contain the 39 HOX genes found in mammals2. Each gene within a cluster is labelled with a number according to their relative position in the chromosome, so for example HOXB1 is the 3’ most member of the B cluster, and HOXB13 is the 5’ most member3. The linkage of genes within each cluster is closely reflected in both their temporal and spatial order of expression in the embryo, with the 3’ genes being expressed more anteriorly and earlier than their 5’ neighbours (Figure 1). The relative position within the cluster is also reflected in the co-factor interactions, DNA binding specificity and regulation of each member2. (more…)

Implementation of flow cytometric biomarker assays in clinical development

Issue 3 2011 / 20 June 2011 / Dianna Y. Wu & Russell Weiner, Clinical Biomarkers and Diagnostics, Merck & Co

Biomarker research has become one of the integral aspects in drug discovery and development. It is broadly utilised to confirm drug mechanism of action (MOA), explore PK/PD correlation, support dose selection and predict response to treatment. Therefore, biomarker data provide valuable information to guide clinical decisions, support drug filings with regulatory agencies and ultimately increase the market value of the drug.

Flow cytometry is a powerful technology for the analysis of multiple biological parameters of individual cells within heterogeneous cell populations. It is widely being used in biomarker research to monitor development and differentiation of cell populations, evaluate target engagement and biomarker expression on/in the cells and assess cell functions and signalling events. (more…)

Reducing attrition in drug discovery: The role of biomarkers

Issue 3 2011 / 20 June 2011 / Sheraz Gul, Vice President & Head of Biology, European ScreeningPort GmbH

The development of most diseases is often attributed to the dysfunction of the activities of key proteins involved in biological processes and their modulation by a therapeutic agent is considered to offer the potential to alleviate the disease state. However, prior to discovering a therapeutic agent, it is usually necessary to identify and validate that a particular protein is the underlying cause of the disease. It is often the case that a single target is implicated as being the cause of more than one disease. This suggests that particular focus needs to be paid to validating these targets for drug discovery purposes as many experimental drugs that are designed to modulate the activity of a specific protein often fail to exhibit efficacy during clinical trials. The role that biomarkers can play in reducing the attrition observed in drug discovery will be discussed in this article. (more…)

Using translational pharmacology biomarkers to drive earlier decision making

Issue 2 2011 / 19 April 2011 / Magnus Ivarsson, Head of Physiological Biomarkers, Pfizer and Mark Fidock, Head of Quantitative Biomarkers, Research Enabling Group, Pfizer

The current high rate of attrition during drug development is unsustainable. An increasing amount of the cost of developing a new drug is made up of the investment in molecules that fail at some point during the process and the later that failure occurs, the more costly it will be. Recent surveys suggest that the attrition rate in the pharmaceutical industry is now more than 90 per cent from the first in human study to launch1-4. Reducing attrition is now one of the key challenges for the pharmaceutical industry, but before exploring potential ways forward, it is necessary to understand what drives the attrition and causes drug candidates to fail during the development process. (more…)

Application of flowcytometry in drug discovery

Issue 6 2010 / 16 December 2010 / Dana Buckman, Senior Scientist, Biomarkers – Translational Research, Pfizer

Flow cytometry can be used to advance our understanding of diseases in multiple ways. Drug effects and dosages can be ascertained in vitro, along with patient selection based on mutations and antigen profiles. Within the Diagnostic Biomarkers group of Translational Research at Pfizer, we are utilising flow cytometry in conjunction with other diagnostic tools to assist in gaining a clearer understanding of drug target biology and to identify patients that would benefit most from a specified drug regimen. (more…)

Biomarkers and targeted therapies in lung cancer… Where do we stand and where will we go?

Issue 6 2010 / 16 December 2010 / Wolfgang M. Brueckl & Joachim Ficker, Department of Internal Medicine 3, Lung Cancer Center and Thomas M. Mundel, Roche Parma AG

Despite innumerable clinical studies in the past three decades with lots of traditional chemotherapeutical drugs and drug combinations, survival in lung cancer has increased by far less than other entities. Research now focuses on inhibitors of tyrosine kinases which have been shown to have a central role in the development of lung cancer. However, as recent developments show, unselected use of those ‘targeted therapies’ is not always effective and may even be harmful to lung cancer patients if given at the wrong time or to the wrong patient. Biomarkers with predictive value will, in future, be of utmost importance for an individualised tumour tailored therapy. In this perspective, we describe the latest developments in EGF-R directed tyrosine kinase inhibitors and other targeted therapies. Additionally, the actual (limited) predictive role of biomarkers is discussed in this context and further directions are pinpointed. (more…)

Next Generation Drug Development Summit: Imaging Biomarkers

Industry news / 9 November 2010 / NG Online News

Large pharma has been seeking new biomarkers for years – all part of their drug discovery process, but often only as an afterthought in the development process. That’s changed over recent years, but by-and-large the bulk of biomarker work remains in the hands of small -to -medium-sized companies whose focused approach is more attuned to biomarkers being a major element of a final product. (more…)