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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

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…

Article 5: The implementation of rapid microbiological methods

1 November 2010 | By Michael J. Miller, President, Microbiology Consultants, LLC

This is the fifth in a series of articles on rapid microbiological methods that will appear in European Pharmaceutical Review during 2010. In my previous four articles, I have provided an overview of the benefits of rapid microbiological methods (RMMs) as compared with conventional methods, validation strategies and regulatory perspectives…

Figure 2 Spray drying. Screenshot of on-line PSD analysis, providing real-time PSD-measurement (top-right) and continuous PSD-monitoring (bottom; d50-orange, d90-blue, d10-green, transmission-red)
Figure 2 Spray drying. Screenshot of on-line PSD analysis, providing real-time PSD-measurement (top-right) and continuous PSD-monitoring (bottom; d50-orange, d90-blue, d10-green, transmission-red)

Applying PAT in pharmaceutical processes

1 November 2010 | By Mario Hellings, Tom Van den Kerkhof, Jeroen Geens and Steve Mehrman, Johnson & Johnson

As cited by the FDA, “Process Analytical Technology (PAT) is a system for designing, analysing, and controlling manufacturing through timely measurements (i.e., during processing) of critical quality and performance attributes of raw and in-process materials and processes with the goal of ensuring final product quality.”1 The main goal of PAT…

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

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 Principle of 2D cell migration assays. (A) A confluent monolayer of cells is mechanically wounded (‘scratch assay’), usually with a sterile pipette tip, leaving two wound edges (dashed lines) separated by a void. Cells at the leading edges quickly assume a polarised morphology and form broad lamellae pointing into the direction of the void. Over time, cells migrate into the void and, eventually, completely close the wound (B). Cell migration is qualitatively assessed by visual inspection and can be quantitated by measuring gap width or by enumeration of cells populating the wound. Images show T98G human glioblastoma cells immediately after wounding (A) or after 24 hours of migration (B). Distance between lines is one millimetre
Figure 1 Principle of 2D cell migration assays. (A) A confluent monolayer of cells is mechanically wounded (‘scratch assay’), usually with a sterile pipette tip, leaving two wound edges (dashed lines) separated by a void. Cells at the leading edges quickly assume a polarised morphology and form broad lamellae pointing into the direction of the void. Over time, cells migrate into the void and, eventually, completely close the wound (B). Cell migration is qualitatively assessed by visual inspection and can be quantitated by measuring gap width or by enumeration of cells populating the wound. Images show T98G human glioblastoma cells immediately after wounding (A) or after 24 hours of migration (B). Distance between lines is one millimetre

Advances in two-dimensional cell migration assay technologies

1 November 2010 | By Andreas Vogt, Department of Pharmacology and Chemical Biology and the University of Pittsburgh Drug Discovery Institute, University of Pittsburgh

Cell motility plays an important role in many human diseases and normal cellular processes. Cell migration is critical for wound healing as cells of the inflammatory system and fibroblasts populate the wound and initiate re-epithelialisation1. On the other hand, unregulated cell migration contributes to cancer cell invasion and metastasis2. Agents…

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

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 Distribution of drugs in vivo depends on various equilibrium and rate processes between compartments
Figure 1 Distribution of drugs in vivo depends on various equilibrium and rate processes between compartments

Bio-mimetic chromatography to predict drug distribution in vivo

29 October 2010 | By Klara Valko, Analytical Chemistry, GlaxoSmithKline Medicines Research Centre

A major concern for the pharmaceutical industry is the high attrition rate (>90 per cent) of potential drug molecules failing during late stages of the drug discovery process. This may be due to lack of efficacy in the clinic, unexpected side effects or unfavourable pharmacokinetics. There is a need for…

Figure 1 Advances in the development of sequencing technologies have resulted in an increase in data output with a dramatic decrease in cost. This graph compares calculated sequencing costs for one complete haploid human genome sequence (23 chromosomes, three billion bases) * estimated from literature ** marketing figures
Figure 1 Advances in the development of sequencing technologies have resulted in an increase in data output with a dramatic decrease in cost. This graph compares calculated sequencing costs for one complete haploid human genome sequence (23 chromosomes, three billion bases) * estimated from literature ** marketing figures

The Sequencing Revolution: enabling personal genomics and personalised medicine

29 October 2010 | By Bhupinder Bhullar, Novartis Institute for Biomedical Research

It has been 10 years since the completion of the first draft of the human genome. Today, we are in the midst of a full assault on the human genetic code, racing to uncover the genetic mechanisms that affect disease, aging, happiness, violence ... and just about every imaginable human…

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

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 Kv values at different pressure settings (centre vials, average from two experiments per pressure setpoint). Symbols represent: upper solid line = curve fit TopLyoTM vial, upper dotted line = curve fit ‘standard serum tubing’ vial, lower solid line = curve fit EasyLyoTM vial, lower dotted line = curve fit ‘standard moulded’ vial.
Figure 1 Kv values at different pressure settings (centre vials, average from two experiments per pressure setpoint). Symbols represent: upper solid line = curve fit TopLyoTM vial, upper dotted line = curve fit ‘standard serum tubing’ vial, lower solid line = curve fit EasyLyoTM vial, lower dotted line = curve fit ‘standard moulded’ vial.

Primary packaging materials for pharmaceutical freeze-drying: Moulded vs. serum tubing vials

19 August 2010 | By Susanne Hibler and Dr. Henning Gieseler, University of Erlangen-Nuremberg, Division ofPharmaceutics, Freeze Drying Focus Group

Pharmaceutical freeze-drying is used to stabilise delicate drugs which are typically unstable in solution over a longer shelf life. The liquid formulation is converted into a solid, highly porous cake which can be easily reconstituted prior to administration. The majority of freeze-dried products in the pharmaceutical industry are used for…

Article 4: The implementation of rapid microbiological methods

19 August 2010 | By Michael J. Miller, President, Microbiology Consultants, LLC

This is the fourth in a series of articles on rapid microbiological methods that will appear in European Pharmaceutical Review during 2010. Believe it or not, today’s regulatory authorities encourage the use of rapid microbiological methods (RMMs), and when applicable, they have put policies in place that provide guidance on…

Figure 1 Comparison between the spectra derived from a 5μm polystyrene bead using either standard Raman spectroscopy (A) or modulated Raman spectroscopy (B)
Figure 1 Comparison between the spectra derived from a 5μm polystyrene bead using either standard Raman spectroscopy (A) or modulated Raman spectroscopy (B)

Raman spectroscopy and cancer cells

19 August 2010 | By Andrew Riches, Professor of Experimental Pathology, School of Medicine, University of St. Andrews and Co-authors: C. Simon Herrington, School of Medicine Kishan Dholakia, Elisabetta Canetta, Antonia Carruthers, Michael Mazilu, Anna Chiara de Luca, School of Physics & Astronomy Chris Goodman, Greg Kata, Nabi Ghulam, Kadi Nourdin, Department of Urology, Ninewells Hospital & Medical School, Dundee

Raman spectroscopy has the potential to provide diagnostic information to the clinician. The technique has a number of advantages allowing individual cells to be interrogated without staining. With further developments in technology, the surgeon will be able to rapidly acquire accurate diagnostic information at the time of operation using fibre…

Figure 1 Packing diagrams showing the different molecular arrangements in polymorphs A (left) and B (right) of the antipsychotic drug risperidone (centre). Unit cell parameters for each polymorph are shown.
Figure 1 Packing diagrams showing the different molecular arrangements in polymorphs A (left) and B (right) of the antipsychotic drug risperidone (centre). Unit cell parameters for each polymorph are shown.

Polymorph screening in pharmaceutical development

19 August 2010 | By Professor Alastair J. Florence, Solid-State Research Group, Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde

The majority of active pharmaceutical ingredients (APIs) are produced by crystallisation and so the phenomenon of polymorphism, whereby an organic molecule can adopt more than one crystalline form (Figure 1), is of considerable importance when trying to achieve consistent product quality during the manufacture of pharmaceutical solids and solid dosage…

Figure 1 openBIS is a software framework for organising and annotating data and metadata from biological experiments, providing query and display functionality, integrating it into data pipelines and sharing it with other researchers
Figure 1 openBIS is a software framework for organising and annotating data and metadata from biological experiments, providing query and display functionality, integrating it into data pipelines and sharing it with other researchers

Towards a comprehensive open source platform for management and analysis of High Content Screening data

19 August 2010 | By Karol Kozak, Angela Bauch, Gabor Csucs,Tomasz Pylak & Bernd Rinn, ETH Zurich

As High Content Screening (HCS) has moved into the mainstream for biological and pharmaceutical investigations, a lag of well integrated pipelines for automated acquisition, management and analysis of HCS results turns out to be a bottleneck for fully leveraging the wealth of information contained in a screen and moving to…