Gastrointestinal stromal tumors (GISTs) express somatostatin receptors and bind radiolabeled somatostatin analogs

Abstract

Peptide receptor-mediated radiotherapy via SSTR may provide a novel treatment strategy in carefully selected GIST patients with TKI-resistant tumors.

International Union of Basic and Clinical Pharmacology. CV. Somatostatin Receptors: Structure, Function, Ligands, and New Nomenclature

“…SST 2 expression was also observed in NETs of other origins, including thymus, breast, cervix, or prostate ( Kajiwara et al, 2009 ; Mizutani et al, 2012 ). Furthermore, SST 2 was detected in 88%–100% of GI stromal tumors (GIST), and, also in this tumor entity, an association with favorable patient outcomes was demonstrated ( Palmieri et al, 2007 ; Arne et al, 2013 ; Zhao et al, 2014 ). Depending on tumor grade and location, SST 2 was observed in 45%–100% of colorectal carcinomas ( Qiu et al, 2006 ; Evangelou et al, 2012 ) and in 41%–67% of HCCs ( Blaker et al, 2004 ; Reynaert et al, 2004 ; Verhoef et al, 2008 ); SST 2 was expressed in 20%–79% of breast cancers ( Pilichowska et al, 2000 ; Orlando et al, 2004 ; Kumar et al, 2005 ; Fischer et al, 2008 ; Lupp et al, 2011 ; Frati et al, 2014 ), in 57% of cervical carcinomas, in 39% of endometrial cancers ( Schulz et al, 2003 ), and in 30% of ovarian carcinomas ( Hall et al, 2002 ; Schulz et al, 2003 ).…”

“…Furthermore, SST 5 was detected in 31%–45% of bronchopulmonary neoplasms ( Kaemmerer et al, 2015a ; Lapa et al, 2016 ) and occasionally also in other tumors with neuroendocrine differentiation ( Mizutani et al, 2012 ). SST 5 was observed in 15%–47% of GIST, and SST 2 and/or SST 5 immunoreactivity was associated with increased recurrence-free survival ( Arne et al, 2013 ; Zhao et al, 2014 ). SST 5 was detected in 39%–70% of colorectal cancers, and expression was higher in well to moderately differentiated tumors than in poorly differentiated ones, with a positive correlation with favorable patient outcomes ( Qiu et al, 2006 ; Evangelou et al, 2012 ).…”

Somatostatin Receptor Avidity in Gastrointestinal Stromal Tumors: Theranostic Implications of Gallium-68 Scan and Eligibility for Peptide Receptor Radionuclide Therapy

“…Gastrointestinal stromal tumors have been reported to express somatostatin receptors and bind radiolabeled somatostatin analogs, with some authors considering the possibility of using such receptors as a new prognostic biomarker and potential therapeutic strategy [ 4 - 5 ]; however, this is the first report describing the utility of gallium-68 DOTATATE for their detection and to suggest PRRT as a potential treatment option for GIST patients. It is unclear if this biomarker feature is specific to SDH-deficient GIST, or if the presence of somatostatin receptors is a common finding in all types of GIST, which seems very plausible.…”

“…Given some pre-clinical data regarding the expression of somatostatin receptors (SSTR) in GISTs as a potential target for a therapeutic strategy [ 4 - 5 ], the patient underwent a gallium-68 DOTATATE scan, which reported significant somatostatin receptor avidity in existing lesions as hypothesized (Figure 1 ), suggesting that this imaging modality may be used as an option for diagnostic and follow-up purposes in GIST patients, similar to the indication of gallium-68 DOTATATE in patients with somatostatin receptor positive neuroendocrine tumors (NETs) [ 6 ].…”

Succinate dehydrogenase-deficient gastrointestinal stromal tumor: from diagnostic dilemma to novel personalised therapy in 2 case reports

“…In considering alternative therapies for patients with TKI refractory or wild-type disease, prior in vivo work has demonstrated that GIST tumours express somatostatin receptors and bind somatostatin analogues, and therefore may respond to peptide radionuclide receptor therapy (PRRT) (20)(21)(22)(23). In 2013, Arne et al demonstrated significant expression of SSTR1 and SSTR2, with low levels of SSTR3-5 in GIST tumours via quantitative PCR.…”