Small molecules

BRAF mutation predicts sensitivity to MEK inhibition. Solit, D. B. et al. Nature 6 Nov 2005 (10.1038/nature04304)

Gain-of-function mutations in Ras or Raf family members are found in most human cancers. Both of these signalling molecules activate the mitogen-activated protein kinase kinase 1 (MAP2K1, also known as MEK)–extracellular regulated kinase (ERK) pathway. This paper shows that tumours with mutations in BRAF are highly and selectively sensitive to small-molecule MEK inhibitors, and offer a rational therapeutic strategy for targeting this genetically defined tumour subtype.

Targeted therapies

Oncogenic pathway signatures in human cancers as a guide to targeted therapies. Bild, A. H. et al. Nature 6 Nov 2005 (10.1038/nature04296)

Bild and colleagues show that gene expression profiles in tumour cells can be identified that reflect the activation status of several oncogenic pathways. These signatures can be used to identify similar patterns of pathway deregulation in a large panel of various human cancers, and these patterns have a prognostic value. Applying the same expression patterns to cancer cell lines predicted their sensitivity to targeted therapies, indicating that these signatures might be a useful guide to choosing targeted therapies in tumour treatment.

Prognostic markers

A microRNA signature associated with prognosis and progression in chronic lymphocytic leukemia. Calin, G. A. et al. New Engl. J. Med. 335, 1793–1801 (2005)

Can microRNA (miRNA) profiles be used as prognostic markers in chronic lymphocytic leukaemia (CLL)? Analysis of 94 samples of CLL cells for the differential expression of 190 miRNA genes identified a 13 gene miRNA expression signature that is associated with prognostic factors and disease progression. Mutations in the miRNA transcripts were common and might have functional importance.

Cellular adhesion

Focal adhesion kinase promotes the aggressive melanoma phenotype. Hess, A. R. et al. Cancer Res. 65, 9851–9860 (2005)

Metastases in malignant melanoma remain a significant barrier in the treatment of this disease. Mary Hendrix and colleagues investigated the function of focal adhesion kinase (FAK) in promoting melanoma metastasis. They found that FAK is phosphorylated on its key tyrosine residues Tyr397 and Tyr576 in aggressive melanomas only, and that this correlates with increased invasive and migrational properties, as well as increased cellular plasticity. Expression of a kinase-dead FAK abrogated these effects, indicating that FAK-mediated signalling pathways might be viable targets in malignant melanoma.