Searchable abstracts of presentations at key conferences in endocrinology
Endocrine Abstracts (2011) 26 S3.1

ECE2011 Symposia Molecular mechanisms in neuroendocrine tumours (3 abstracts)

Somatostatin and dopamine signalling in neuroendocrine tumours

Diego Ferone


Center of Excellence for Biomedical Research, University of Genoa, Genoa, Italy.


The discovery of the new properties of somatostatin (SSTRs) and dopamine (DRs) receptors has led to a renewed interest in agents targeting these receptors, and has opened new perspectives for medical treatment of patients with neuroendocrine tumors (NETs). Indeed, patients unresponsive or resistant to the ‘classical’, currently available somatostatin analogs may benefit from these insights. Moreover, SSRs and DRs crosstalk at membrane level may trigger alternative intracellular pathways, or even enhance the signalling for the control of cell growth. However, the activity of SSTRs and DRs could be also driven by the specific cell types in which they are expressed, and the formation of receptor dimers on cell membrane may similarly vary, depending on the cells, rather than the receptors profile. Therefore, not only the receptor profiles but also the cell types, as well as the dimerization, are responsible for the final effect of a given ligand.

New somatostatin analogs and hybrid molecules, which display a broader and different spectrum of activities compared to conventional analogs, seem to be a promising therapeutic alternative for the control of hormone secretion and, hopefully, to reduce tumor burden. Few initial in vitro studies revealed that individual NETs exhibit substantially different SSTRs and DRs expression, which are differently coupled to the intracellular signalling pathways. Indeed, individual NETs seem to respond differently to specific somatostatin analogs, panagonists, and new SSTR/DR chimeric compounds, depending on the SSTR and DR profile coupling to signalling pathways. Although antiproliferative effects seem mainly driven by ERK1/2 activation, additional intracellular pathways, such as JNK signalling and other proteins involved in the control of cell cycle may be targeted.

The crucial point emerging from these preliminary studies is that when, in the future, a therapeutic strategy is conceived, it will require a stronger and adequate delineation of the specific receptor profile, as well as a clarification of the linked intracellular pathways of the tumor, in order to optimize an effective treatment.

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