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Biomarkers

 

Flow Cytometry
Flow Cytometry
article

Implementation of flow cytometric biomarker assays in clinical development

20 June 2011 | By 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…

Sheraz Gul
Sheraz Gul
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Reducing attrition in drug discovery: The role of biomarkers

20 June 2011 | By 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.

AstraZeneca announces collaborations to use CRISPR technology for genome editing across its drug discovery platform
AstraZeneca announces collaborations to use CRISPR technology for genome editing across its drug discovery platform
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Using translational pharmacology biomarkers to drive earlier decision making

19 April 2011 | By 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.…

Figure 1 A: Control B: Docetaxel treated Induction of apoptosis with Docetaxel compared to untreated. The lower right quadrant represents cells in early apoptosis and cells in the upper right quadrant are cells in late apoptosis due to PI entering the cells through leaky membranes. C: Control D: Docetaxel treated Cell cycle of control cells and Docetaxel treated cells. The first peak shows cells in G0/G1 and the second peak is cells in G2/M. The breast cancer cell line, MDA MB231, was treated with 10nM docetaxel or DMSO control for 72 hours. Cells were harvested, the nuclei isolated and stained with PI. Samples were run on the LSR II flow cytometer and analyed in FCS Express software. Docetaxel arrests the cells in G2/M
Figure 1 A: Control B: Docetaxel treated Induction of apoptosis with Docetaxel compared to untreated. The lower right quadrant represents cells in early apoptosis and cells in the upper right quadrant are cells in late apoptosis due to PI entering the cells through leaky membranes. C: Control D: Docetaxel treated Cell cycle of control cells and Docetaxel treated cells. The first peak shows cells in G0/G1 and the second peak is cells in G2/M. The breast cancer cell line, MDA MB231, was treated with 10nM docetaxel or DMSO control for 72 hours. Cells were harvested, the nuclei isolated and stained with PI. Samples were run on the LSR II flow cytometer and analyed in FCS Express software. Docetaxel arrests the cells in G2/M
article

Application of flow cytometry in drug discovery

16 December 2010 | By 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…

Figure 1 Key signaling pathways of Epidermal Growth Factor Receptor (EGFR). The epidermal growth factor receptor (EGFR) is a member of the human epidermal growth factor receptor (HER) superfamily of receptors comprising of four distinct however structurally similar tyrosine kinase receptors. Upon ligand binding (e.g. EGF, TGF-α) EGFR dimerises with another receptor and undergoes phosphorylation of its TK domain. Activated EGFR stimulates cell proliferation, survival, migration, adhesion and differentiation. EGFR is associated with increased or inappropriate signaling in NSCLC and is a key mediator of tumor progression. Activating mutations of the EGFR kinase domain result in ligand-independent activation of the pathway. Tyrosine kinase inhibitors, such as erlotinib and gefitinib, interfere with the kinase activity of the gene and prevent downstream signaling. Therefore, EGFR is an important target for NSCLC treatment. Modified from Gazdar et al22
Figure 1 Key signaling pathways of Epidermal Growth Factor Receptor (EGFR). The epidermal growth factor receptor (EGFR) is a member of the human epidermal growth factor receptor (HER) superfamily of receptors comprising of four distinct however structurally similar tyrosine kinase receptors. Upon ligand binding (e.g. EGF, TGF-α) EGFR dimerises with another receptor and undergoes phosphorylation of its TK domain. Activated EGFR stimulates cell proliferation, survival, migration, adhesion and differentiation. EGFR is associated with increased or inappropriate signaling in NSCLC and is a key mediator of tumor progression. Activating mutations of the EGFR kinase domain result in ligand-independent activation of the pathway. Tyrosine kinase inhibitors, such as erlotinib and gefitinib, interfere with the kinase activity of the gene and prevent downstream signaling. Therefore, EGFR is an important target for NSCLC treatment. Modified from Gazdar et al22
article

Targeted therapies in lung cancer and Biomarkers

16 December 2010 | By 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…

Figure 3 A multi-omics approach for the discovery and validation of biomarkers to probe multidimensional phases of disease biology. A robust biomarker discovery, development and validation effort must bring together multiple ‘omics’ technologies, data types, databases and bioinformatics and biostatics to identify the most predictive biomarkers across DNA, RNA, protein, phenotype and metabolite domains
Figure 3 A multi-omics approach for the discovery and validation of biomarkers to probe multidimensional phases of disease biology. A robust biomarker discovery, development and validation effort must bring together multiple ‘omics’ technologies, data types, databases and bioinformatics and biostatics to identify the most predictive biomarkers across DNA, RNA, protein, phenotype and metabolite domains
article

Biomarkers in drug discovery and development

1 November 2010 | By Attila A. Seyhan.Translational Immunology, Inflammation and Immunology, Pfizer

Robust and validated biomarkers are needed to improve diagnosis, monitor drug activity and therapeutic response and guide the development of safer and targeted therapies for various chronic diseases. While different types of biomarkers have been impactful in the field of drug discovery and development, the process of identifying and validating…

Figure 1 Schematic of workflow for MALDI MS imaging from slicing fresh tissue to image
Figure 1 Schematic of workflow for MALDI MS imaging from slicing fresh tissue to image
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MS-based clinical proteomics: biomarker discovery in men’s cancer

29 October 2010 | By Brian Flatley Dept of Chemistry, University of Reading, Reading and Harold Hopkins Dept of Urology, Royal Berkshire NHS Foundation Trust Hospital, Reading and Peter Malone Harold Hopkins Dept of Urology, Royal Berkshire NHS Foundation Trust Hospital, Reading and Rainer Cramer Dept of Chemistry, University of Reading, Reading

Each year, approximately 10,000 men in the UK die as a result of prostate cancer (PCa) making it the third most common cancer behind lung and breast cancer. Worldwide, more than 670,000 men are diagnosed every year with the disease. Current methods of diagnosis of PCa mainly rely on the…

Drug Discovery and Development
Drug Discovery and Development
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Novel medicines development for cancer treatment

24 June 2010 | By Hans Winkler, Global Head Oncology & Biomarker Programs, Ortho Biotech Oncology Research & Development, Johnson & Johnson

The pharmaceutical industry has reached a critical phase in its evolution. The cost and time to develop novel medicines has become unsustainable3. Reasons for this may include a much higher demand on evidence of safety and efficacy, rapidly increasing costs of contract research and the tremendous pressure on pricing and…

DNA sequencing
DNA sequencing
article

Applying statistical inference in genomics with evidence based pathways: Towards elucidating new functional correlations of biomarkers

22 February 2010 | By Peter Ghazal, Professor of Molecular Genetics and Biomedicine, University of Edinburgh and Head of Division of Pathway Medicine and Associate Director of Centre for Systems Biology, Edinburgh, Al Ivens, Head of Data Analysis, Fios Genomics Ltd and Thorsten Forster, Statistical Bioinformatician, Division of Pathway Medicine, University of Edinburgh

In conventional pharmacogenomic studies, genetic polymorphisms (including single nucleotide and copy number variations) are elucidated from case-control distribution of individuals usually representing ethnicity, severity of disease, and positive or negative response to treatment. However, the interpretation of a single genetic marker in this context is complicated, as the same marker…

article

Sleep changes as translational pharmacodynamic biomarkers

9 October 2009 | By

Pharmacodynamic biomarkers in drug discovery: Developing a new drug is an expensive and time-consuming business1-3. A substantial part of the overall cost of drug development is the investment in molecules that fails at some point during the development process and it is necessary to identify these compounds as early as possible.…