Therapy for glioblastoma: is it working?

Glioblastoma (GBM) remains one of the most intransigent of cancers, with a median overall survival of only 15 months after diagnosis. Drug treatments have largely proven ineffective; it is thought that this is related to the heterogeneous nature and plasticity of GBM-initiating stem cell lineages. Although many combination drug therapies are being positioned to address tumour heterogeneity, the most promising therapeutic approaches for GBM to date appear to be those targeting GBM by vaccination or antibody- and cell-based immunotherapy. We review the most recent clinical trials for GBM and discuss the role of adaptive clinical trials in developing personalised treatment strategies to address intra- and inter-tumoral heterogeneity.

Overview of chemical genomics and proteomics.

Chemical genetics, genomics, and proteomics have been in existence as distinct offshoots of chemical biology for about 20 years. This review provides a brief definition of each, followed by some examples of how each technology is being used to advance basic research and drug discovery.

Drug discovery in the era of Facebook--new tools for scientific networking.

Social networking is beginning to make an impact on the drug discovery process. While bioinformatics and chemoinformatics underpin research at a scientific level, rapid communication between individual researchers across continents now allows the global exchange of ideas, tools and technologies. Networking at this level of speed and reach is quite a recent phenomenon. It facilitates the development of common interests, accelerates technology transfer and increases cooperative and competitive behaviour. In this review, we critically evaluate different web based networking approaches as effective resources for the drug discovery scientist. We also ask whether social networking sites will evolve into serious and credible resources for the drug discovery community.

The emergence of chemical genomics in drug discovery.

The interaction of small organic molecules with proteins and other macromolecules is fundamental to drug action. Chemical genomics employs a combination of chemistry, genomics and informatics to study these drug-target interactions in a systematic and global manner in order to improve the efficiency of the drug discovery process.

Probes for chemical genomics by design.

Chemical genomics represents a convergence of biology and chemistry in the era of global approaches to target identification and intervention. The success of genomics has led to a bottleneck in target validation that could be overcome by using small diverse organic compounds to interfere with biological processes. Because of the limitations of existing compound collections, this diversity can only fully be exploited using in silico design techniques to guide the selection of molecules with optimal binding properties. Structure-based design is used to create structures de novo that can be synthesized for use as chemical probes and drug leads.

The use of chemical design tools to transform proteomics data into drug candidates.

The Human Genome Project has fueled the massive information-driven growth of genomics and proteomics and promises to deliver new insights into biology and medicine. Since proteins represent the majority of drug targets, these molecules are the focus of activity in pharmaceutical and biotechnology organizations. In this article, we describe the processes by which computational drug design may be used to exploit protein structural information to create virtual small molecules that may become novel medicines. Experimental protein structure determination, site exploration, and virtual screening provide a foundation for small molecule generation in silico, thus creating the bridge between proteomics and drug discovery.