TARGETS最新文献

Arrays of antibodies and of other types of ligand-binding molecule (e.g. protein scaffolds or aptamers) provide a means for rapid detection of proteins and other analytes in multiple samples and ultimately for screening the human proteome in health and disease. The chief reasons for using an array-based approach to diagnostics and proteomics relate to the advantages associated with parallelisation, miniaturisation and automation. The current generation of antibody microarrays promises to perform well as diagnostic tools and for limited protein profiling, using relatively small numbers of available antibodies. Sensitivity, specificity and signal-to-noise ratios in the multiplex format are major issues and will become more critical as the complexity of arrays is increased. This review describes progress in solving problems associated with the construction of antibody arrays.

The most effective targeted cancer therapies have arisen from research into genetically altered oncogenes, including BCR-ABL, HER2, RAS and EGFR. Recent advances in cancer genetics have identified many regions of the genome that undergo amplification (increase in copy number) but, in most cases, the key oncogenic targets driving the growth and survival of cancer cells remain unknown. In this review, we discuss high-throughput technologies for the discovery of putative oncogenes, and clinical and functional validation of these genes as targets for therapy. New technologies in translational genomics facilitate the identification, validation and prioritization of candidate molecular targets for anti-cancer therapy.

Evasion of the checks and balances that govern the human cell division cycle lies at the heart of all proliferative diseases. Because of the astonishing variety of ways that cancer cells manage to achieve growth advantages over normally proliferating cells, it can be expected that pharmacological reinstatement of cell cycle progression control should also be achievable in a multitude of ways. Very few cell cycle targets have so far been exploited for the discovery of mechanism-based anticancer drugs; even fewer targets have yielded actual or experimental clinical drugs. Here, we discuss the approaches that have been and are beginning to be used to identify and validate molecular targets whose pharmacological modulation holds the promise of nongenotoxic and inherently selective cancer therapy. We discuss an approach based on using the genetically amenable organism Drosophila melanogaster as a model for the identification of cell cycle targets, particularly those involved in the processes of mitosis.

Patent Update is a regular column dedicated to the complex issues that affect patents in the genomics and proteomics field. In each issue, there are two sections compiled by patent attorneys. The first section, Patents – a Practical Perspective, is a commentary on current issues, landmark patents, useful patent resources and how to search them, and legislative changes that impact the pharma and biotech industries. The second section, Patent News, provides brief synopses of recently issued patents and other patent events, and their significance to drug discovery R&D.

The process of deriving accurate annotations for genes in newly sequenced genomes has up to now been based largely on projection of results in one organism to genes in other organisms based on sequence similarity. We are now entering a period in which metabolic reconstructions will play an increasingly significant role. These reconstructions will support a gradual refinement of estimates of function, leading to more consistent and precise understanding. They will become key components in establishing which functional roles have not yet been connected to genes and which aspects of an organism's physiology can be understood in terms of existing functional assignments. As each refinement is made, we incrementally approach the goal of establishing a qualitative understanding of an organism in terms of its inventory of genes.