Anticancer drugs

Gefitinib-sensitizing EGFR mutations in lung cancer activate anti-apoptotic pathways. Sordella, R. et al. Sciencexpress 29 Jul 2004 (doi:10.1126/science.1101637)

Recent findings associating clinical responses in non-small-cell lung cancers (NSCLCs) to the drug gefitinib (Iressa; AstraZeneca) — which inhibits the tyrosine kinase activity of the epidermal growth factor receptor (EGFR) — with activating mutations within the EGFR kinase domain have attracted considerable attention. Sordella et al. now provide insight into the underlying mechanism by showing that these mutant EGFRs selectively transduce survival signals on which NSCLCs become dependent.

Neurological disorders

P2X7 receptor inhibition improves recovery after spinal cord injury. Wang, X. et al. Nature Med. 10, 821–827 (2004)

Treatments for spinal cord injury represent a major unmet medical need. Wang and colleagues show that spinal cord injury is associated with prolonged purinergic receptor activation that results in excitotoxicity-based neuronal degeneration, and that the inhibition of this process with antagonists of the P2X7 purine receptor can improve functional recovery after spinal cord injury.

Imaging

In vivo cancer targeting and imaging with semiconductor quantum dots. Gao, X. et al. Nature Biotechnol. 22, 969–976 (2004)

The development of highly sensitive and specific probes that lack the inherent limitations of organic dyes and fluorescent proteins could be valuable in molecular imaging and medical diagnostics. Gao et al. describe the development of nanoparticle probes based on semiconductor quantum dots that are suitable for in vivo targeting and imaging of human prostate cancer cells growing in mice.

Biotechnology

Discovery of an allosteric site in the caspases. Hardy, J. A. et al. Proc. Natl Acad. Sci. USA 16 Aug 2004 (doi:10.1073/pnas.0404781101)

Allosteric regulation of proteins by conformational change is a key means of biological control, but identifying and characterizing novel allosteric sites — which might provide opportunities to develop small molecules that therapeutically regulate protein function — has proved challenging. Hardy and colleagues describe the application of an approach known as 'Tethering', which is based on the reversible formation of disulphide bonds between thiol-containing small molecules and accessible cysteine residues in protein targets, to identify a novel allosteric site in caspases, which are promising drug targets owing to their key role in apoptosis and inflammation.