Molecular strategies and 111in-labelled somatostatin analogues in defining the management of neuroendocrine tumour disease: a new paradigm for surgical management.
This manuscript provides a gene-chip examination of gastric ECL cell proliferation in an animal model of neuroendocrine tumour disease. Data that were used to identify molecular targets were then utilised to develop novel therapeutic strategies as appropriate adjuncts to surgery in human disease. Alterations in growth-mediated cell signaling (the AP-1 pathway) and in the cell cycle were identified in ECL cell tumours in the animal model and confirmed in human tumour tissue. The growth-inhibitory somatostatin receptor subtype 2 was identified as a potential clinical target. An investigation of patients with neuroendocrine tumours treated using SSTR2 targeted radiotherapy [111In]pentetreotide producing encouraging preliminary results. Fifty-six per cent of patients with evaluable hormone markers demonstrated stable levels or a significant decrease in one or more measured markers. This data demonstrate that gene pathways recognised to be altered in an animal model of a human disease can be used to identify therapeutic agents. This approach was successfully used to discover novel strategies that can be both effective and appropriate adjuncts to surgery for patients with neuroendocrine tumour disease.
Modlin
I M
IM
Department of Surgery, Yale University School of Medicine, 333 Cedar Street, P.O. Box 208062 New Haven, Connecticut 06520-8062, USA.
Kidd
M
M
Hinoue
T
T
Lye
K D
KD
Murren
J
J
Argiris
A
A
D000818:Animals; D002453:Cell Cycle; D049109:Cell Proliferation; D030541:Databases, Genetic; D004195:Disease Models, Animal; D016503:Drug Delivery Systems; D004759:Enterochromaffin Cells / Q000502:physiology*; D020869:Gene Expression Profiling; D006801:Humans; D007205:Indium Radioisotopes; D009115:Muridae; D018358:Neuroendocrine Tumors / Q000000981:diagnostic imaging / Q000235:genetics* / Q000601:surgery*; D020411:Oligonucleotide Array Sequence Analysis; D011877:Radionuclide Imaging; D017481:Receptors, Somatostatin / Q000235:genetics / Q000502:physiology; D013004:Somatostatin / Q000032:analysis* / Q000235:genetics*
D007205:Indium Radioisotopes; D017481:Receptors, Somatostatin; D013004:Somatostatin; C093733:somatostatin receptor 2