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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
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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
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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…

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Functional genomics as a tool for guiding personalised cancer treatment

29 October 2010 | By Roderick Beijersbergen, Group Leader Molecular Carcinogenesis, the Netherlands Cancer Institute

Improved understanding of the molecular alterations in cancer cells has fuelled the development of more specific and directed cancer therapies. However, it has become clear that response rates can be low due to confounding genetic alterations that render these highly specific therapies ineffective. As a result, the costs of cancer…

Figure 1 siRNA drug discovery pipeline
Figure 1 siRNA drug discovery pipeline
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The evolution of RNAi technologies in the drug discovery business

29 October 2010 | By Jason Borawski and L. Alex Gaither, Novartis Institutes for Biomedical Research

In the past decade, the pharmaceutical industry has exploited the naturally occurring cellular RNAi pathway to enhance drug discovery research. The RNAi pathway, triggered by dsRNA, selectively, although not always specifically, degrades mRNA leading to substantial decreases in post-transcriptional gene expression1. Researchers have capitalised on this intrinsic pathway by synthesising…

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…

Figure 1 ASSET™ plan and detail Copyright: The Automation Partnership
Figure 1 ASSET™ plan and detail Copyright: The Automation Partnership
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High content cell based primary screening for oncology targets – a perspective

25 June 2010 | By Peter Alcock, Colin Bath, Carolyn Blackett & Peter B. Simpson, Screening & Assay Sciences, Cancer Bioscience, AstraZeneca Alderley Park

Over the last 15 years, vendors have offered microscope-based instruments capable of producing images of fluorescent labelled components of cells grown in microtitre plates. These instruments are typically bundled with analysis software capable of defining the relative distribution of several fluorescent markers on a cell by cell basis1,2. As 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…

Figure 1 Targeting viral-associated RNAs at different stages of infection. Step 1, targeting of incoming RNA; step 2, targeting of viral mRNAs following provial integration; and step 3, targeting viral outgoing pregenomic template DNA.
Figure 1 Targeting viral-associated RNAs at different stages of infection. Step 1, targeting of incoming RNA; step 2, targeting of viral mRNAs following provial integration; and step 3, targeting viral outgoing pregenomic template DNA.
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RNAi-based therapies for the treatment of HIV

24 June 2010 | By Marc S. Weinberg and Fiona van den Berg, Antiviral Gene Therapy Research Unit, Department of Molecular Medicine and Haematology, University of Witwatersrand

Since the discovery of RNA interference (RNAi) in 1998 and the demonstration of RNAi in mammalian cells in 2001, research into the mechanisms and applications of this pathway has moved swiftly. RNAi is capable of mediating potent and specific silencing of genes and has therefore shown promise in the development…

Figure 1 MD simulation model of the opsin-transducin complex in a POPC lipid bilayer. Opsin and transducin are drawn in ribbon format and post-translational modification on opsin and transducin are represented in space-fill style. Opsin is oriented in the bilayer such that helix 4 (H4) is perpendicular to the plane of the bilayer. The extracellular surface is oriented toward the top of the figure.
Figure 1 MD simulation model of the opsin-transducin complex in a POPC lipid bilayer. Opsin and transducin are drawn in ribbon format and post-translational modification on opsin and transducin are represented in space-fill style. Opsin is oriented in the bilayer such that helix 4 (H4) is perpendicular to the plane of the bilayer. The extracellular surface is oriented toward the top of the figure.
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Examining receptor activation: New technologies reveal how G protein-coupled receptors recognise ligands and talk to intracellular partners

24 June 2010 | By Thomas P. Sakmar, Laboratory of Molecular Biology & Biochemistry, Rockefeller University

Heptahelical G protein-coupled receptors (GPCRs) are arguably the most important single class of pharmaceutical drug targets in the human genome. According to Overington, of the 266 human targets for approved drugs, a remarkable 27 per cent correspond to rhodopsin-like, or Family A, GPCRs. Despite recent dramatic advances in targeting of…

DNA sequencing
DNA sequencing
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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…

Professor Conan Fee, University of Canterbury, New Zealand
Professor Conan Fee, University of Canterbury, New Zealand
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Protein PEGylation: An overview of chemistry and process considerations

22 February 2010 | By ,

Innovative drug delivery technologies are key components of drug development, with commercial and intellectual values. PEGylation is an excellent example of a delivery system that has scientific and multi-billion dollar commercial importance due to the remarkable improvement in the circulatory half lives of therapeutics, especially for proteins and peptides but…

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RNAi screening in the era of high-throughput genetics

12 December 2009 | By

The use of RNAi screening to identify potential drug targets has enjoyed great success in recent years as a robust method for linking genes to a disease process through a functional assessment of a gene in an experimental model1. True, RNAi screening is complicated by problems such as off-target effects…