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Annals of Oncology Advance Access originally published online on February 13, 2007
Annals of Oncology 2007 18(8):1307-1313; doi:10.1093/annonc/mdm009
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© 2007 European Society for Medical Oncology

reviews

New drug development in digestive neuroendocrine tumors

I Durán1, R Salazar2,*,{dagger}, O Casanovas3, V Arrazubi2,3, E Vilar4, LL Siu1, J Yao5 and J Tabernero4

1 Department of Medical Oncology and Hematology, Princess Margaret Hospital, University Health Network, Toronto, Canada
2 Department of Medical Oncology
3 Translational Research Laboratory, Institut Català d'Oncologia
4 Department of Medical Oncology, Vall d'Hebron University Hospital, Barcelona, Spain
5 Gastro-Intestinal Unit, MD Anderson Cancer Center, University of Texas, Texas, USA

* Correspondence to: Dr R. Salazar, Department of Medical Oncology, Institut Català d'Oncologia, Avenue Gran Via s/n, 08907, Barcelona, Spain. Tel: +34 93 2607500; Fax: +34 93 2607741; E-mail: ramonsalazar{at}iconcologia.net

The traditional cytotoxic agents are of limited efficacy in the treatment of neuroendocrine tumors of the gastrointestinal tract (NETs). Recent investigations have brought up a number of biological features in this family of neoplasms that could represent targets for anticancer treatment. NETs seem to have an extraordinary tumor vascularization with high expression of proangiogenic molecules such as the vascular endothelial growth factor along with overexpression of certain tyrosine kinase receptors such as the epidermal growth factor receptor (EGFR), the insulin growth factor receptor (IGFR) and their downstream signaling pathway components (PI3K-AKT-mTOR). The rationale of an antiangiogenic approach in the treatment of NETs and the use of other pharmacological strategies such as EGFR, IGFR and mammalian target of rapamycin inhibitors are discussed. Additionally, the emerging results of recent clinical trials with these targeted drugs are presented.

Key words: antiangiogenic therapies, carcinoid tumors, EGFR inhibitors, mTOR inhibitors, neuroendocrine tumors, targeted drug therapy

{dagger} Chairman of the Spanish Task Force Gastrointestinal NETs group.

Received for publication November 18, 2006. Accepted for publication November 27, 2006.


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