Protein Kinases

Tumour cell and endothelial cell therapy of oral cancer by dual tyrosine kinase blockade. Yigitbasi, O. G. et al. Cancer Res. 64, 7977–7984 (2004)

Activation of the epidermal growth factor (EGF) signalling pathway is associated with the progressive growth of head and neck cancer. The tyrosine-kinase inhibitor AEE788 blocks EGF and vascular endothelial growth factor signalling pathways, so the authors investigated its efficacy in inhibiting the growth of two human head and neck cancer cell lines injected into nude mice. AEE788 significantly inhibited tumour-cell growth and induced apoptosis in both endothelial and tumour cells. So, patients with head and neck cancer should be included in clinical trials of AEE788.

Immunology

SOCS1 is a key brake of antigen presentation by dendritic cells and restricts anti-tumour immunity. Shen, L. et al. Nature Biotechnol. 21 Nov 2004 (doi:10.1038/nbt1035)

The successes so far for tumour vaccines have been limited, for many and various reasons. In this paper the authors show that the suppressor of cytokine signalling 1 (SOCS1) is a key regulator of antigen presentation by dendritic cells. Silencing SOCS1 expression strongly enhances antigen-specific antitumour immunity.

Therapeutics

A polymer library approach to suicide gene therapy for cancer. Anderson, D. G. et al. Proc. Natl Acad. Sci. USA 101, 16028–16033 (2004)

Effective suicide-gene therapy requires that a toxin is delivered to tumours with little effect on normal cells. One huge hurdle is finding a vector that is itself non-toxic; Sawacki and co-workers are investigating biodegradable poly(β-amino esters) as alternatives to viral vectors or non-viral systems. They screened a library of more than 500 biodegradable poly(β-amino esters) and identified one — C32 — that is non-toxic and avoids gene expression in healthy muscle, and is highly efficient at delivering DNA to tumour cells.

Angiogenesis

Requirement for sphingosine 1-phosphate-1 in tumor angiogenesis demonstrated by in vivo RNA interference. Chae, S. -S. et al. J. Clin. Invest. 114, 1082–1089 (2004)

Angiogenesis requires the lipid mediator sphingosine 1-phosphate (S1P) and its receptor S1P1. Chae et al. show that S1P1 is strongly induced in tumour vessels, and, using small interfering RNA (siRNA) for S1P1, that downregulation of S1P1 suppresses vascular stabilization, angiogenesis and tumour growth in vivo. The authors suggest that S1P1 siRNA might provide a novel therapeutic approach for the control of pathogenic angiogenesis.