SSTR2 expression

In ONB, relative to SNUC and SNEC, the SSTR2 expression profile, combined with its immune profiles, indicates potential novel therapeutic strategies and combinations for this unmet clinical need. Conversely, the inflammatory microenvironment of SNUC may be targetable using immuno-oncologic therapies.

NPC is a rare malignancy with significant geographical variations in incidence rates. Somatostatin receptor 2 (SSTR2) expression in NPC is well documented and can serve as a potential theragnostic marker in advanced NPC where the successful outcome is minimal with currently available treatment modalities.

[225Ac]Ac-EBTATE is safe and effective against SCLC and pan-NET and therefore warrants clinical investigation.

However, postoperative histological studies suggested that the intracellular domain of SSTRs were highly expressed, while the extracellular domain may be mutated. We present a rare case of insulinoma expressing an aberrant form of SSTRs resulting in a discrepancy between the preoperative octreotide assessment and postoperative SSTR expression.

P1/2, N=0, Withdrawn, University of Chicago | N=52 --> 0 | Trial completion date: Feb 2027 --> Sep 2024 | Recruiting --> Withdrawn | Trial primary completion date: Feb 2027 --> Sep 2024

Both, AdFITC(E2)-CAR T-cell tumor infiltration and biocidal activity were Octo-Fluo concentration-dependent, with high doses of Octo-Fluo, saturating both the CAR and the SSTR2 antigen independently, leading to the loss of tumor infiltration and biocidal activity due to the loss of bridge formation. Our findings demonstrate the potential of using AdFITC(E2)-CAR T-cells with Octo-Fluo as a versatile, on-off tunable bispecific adaptor for targeted CAR T-cell immunotherapy against SSTR2-positive NETs.

Although brain metastases are rare in the cancers with approved targeted radionuclide therapies, there is no a priori reason to assume that such treatments would not be effective against brain metastases if the targets are expressed and not shielded by the blood brain barrier. Here, we discuss the current state of the art and opportunities of targeted radionuclide therapies for patients with brain and leptomeningeal metastases.

Upon enrollment, the patient received two rounds of the radiolabeled somatostatin analogue lutetium-177 octreotate (177Lu-DOTATATE), which was well tolerated...The observed variation in SSTR2 expression between tumor lesions suggests that heterogeneous target expression may have been the reason for treatment failure in this patient's case. Further investigation within the LuDO-N trial will give a more comprehensive understanding of the correlation between SSTR2 expression levels and treatment outcomes, which will be important to advance treatment strategies based on MRT for children with high-risk NB.

In patients with SCLC, SSTR2 expression assessed by 68Ga-SSO120 PET and by IHC were closely correlated and associated with shorter survival. More than 75% of patients showed higher whole-body 68Ga-SSO120 tumor uptake than liver uptake and almost 40% high or very high uptake, possibly paving the way towards theranostic applications.

We treated cells derived from 23 NF-PitNETs with ITF2984, and a subset of them with octreotide, pasireotide (SRLs with high affinity for SSTR2 or 5, respectively), or cabergoline (DRD2 agonist) and we measured cell proliferation and apoptosis. In our model, SSTR3 expression levels did not correlate with ITF2984 antiproliferative nor proapoptotic effects. In conclusion, our data support a possible use of ITF2984 in the pharmacological treatment of NF-PitNET.

Hyponatremia is the dominant clinical features of SN. Preoperative imaging suggests that growth toward the dorsal region is the imaging feature of SN. SSTR2 expression and LMCD1-AS1:GRM7-AS1 fusion gene event expected to become a new molecular marker for SN. Somatostatin receptor ligand therapy may be a potential therapy for SN.

In contrast to the more commonly used external beam radiation, we explored the feasibility of combining chimeric antigen receptor (CAR) T cell therapy with targeted radionuclide therapy (TRT), which is achieved by delivering β-emitting 177Lu-DOTATATE to tumor via tumor-infiltrating CAR T cells that express somatostatin receptor 2 (SSTR2)...However, this higher dose led to cell death in both the tumor and CAR T cells. Our study suggests that there may exist an optimum range of TRT dosage that can enhance T cell activity and sensitize tumor cells to T cell killing, which may result in more durable tumor control compared to a higher radiation dose.

PD-L1 expression and CD8 + T cell infiltration, either independently or combined with SSTR2 expression and T2WI-MRI intensity, could form a predictive model guiding clinical decisions on fg-SRL employment. Furthermore, targeting PD-L1 through immunotherapy and embracing second-generations of SRL with higher affinity to SSTR5 represent promising strategies to tackle fg-SRL resistance in somatotropinomas.

Raising awareness of OHSS due to functioning gonadotroph tumors is crucial to prevent unnecessary ovarian surgery. Comprehensive histological analysis may provide useful information to better understand the characteristics of functioning gonadotroph tumors.

Furthermore, SSTR2 expression can be used as prognostic factors. When metastatic disease occurs, SSTR2 expression can be used a possible target for somatostatin analogues.

We focused on assessing whether pretreating cells with inhibitors for phosphatidylinositol 3-kinase (PI3K) and mammalian target for rapamycin (mTOR) could enhance the antiproliferative effects of lanreotide...Additionally, combination treatment consisting of BYL719 and everolimus plus lanreotide tested in NCI-H720 and NCI-H727 led to diminished cell proliferation in a dose-dependent manner...Interestingly, SSTR expression reinduction could be exploited in therapeutic and diagnostic applications. The overall results of this study support the evaluation of combination-based therapies using lanreotide in preclinical studies to further increase its antiproliferative effect and ultimately facilitate its use in high-grade tumors.

P1/2, N=52, Recruiting, University of Chicago | Phase classification: P2 --> P1/2

The sAOT is a good predictor tool for assessing response to SRLs and correlates with tumor E-cadherin and SSTR2 expression. Thus, it can be useful in clinical practice for therapeutic decision-making in patients with acromegaly.

Advances in the realm of SSTR2 investigation within HNSCC, with a specific spotlight on laryngeal squamous cell carcinomas (LSCC), tongue squamous cell carcinomas (TSCC), and nasopharyngeal carcinomas (NPC), have been established. This study aims to provide a comprehensive overview of SSTR2 expression patterns, prognostic implications, distinctive signaling pathways, epigenetic modifications, and potential therapeutic strategies associated with SSTR2 in HNSCC.

[ Ga]Ga-DOTA-JR11 PET/CT provided high image quality and presented an ideal diagnostic performance in detecting meningioma and evaluating the involvement of the pituitary and bone. The study provides valuable evidence for the use of [ Ga]Ga-DOTA-JR11 PET/CT as a complementary imaging modality to CE-MRI in the evaluation of meningiomas.

To conclude, tumoral uptake levels of radiolabeled DOTA-TATE were not enhanced after HDACi treatment in vivo, but, depending on the applied inhibitor, increased SSTR2 expression levels were observed.

Our data suggest that PPY-H originates in the lining of pancreatic ducts. Confirmation of SSTR2 in PPY-H, using immunohistochemistry, suggests the utility of Tc EDDA/Hynic-TOC or Ga-DOTA radiotracers in clinical diagnostics; however, studies with larger cohort are needed.

Although our predictive model should be validated in prospective studies, our data suggest that this nomogram may represent an easy-to-use tool, for early predicting the fg-SRLs outcome.

EBV associated NPC showed stronger expression of SSTR2 comparing to HNSCC in other subsites. No significant difference in F18-FDG PET/CT parameters between EBV positive NPC and other types of HNSCC. Future directions would include assessing the role of Cu 64 -DOTATATE PET/MRI in evaluation of EBV positive NPC and its impact on radiation therapy planning.

We demonstrate the feasibility of in vivo CART tracking using somatostatin-analog PET, as well as the augmentation of CART cell localization to tumor and systemic expansion following PRRT therapy, whereby tumor killing by targeted radiation enhances additional CART trafficking to tumor. We further provide additional validation for PSMA as a potential theranostic target in GBM. Future studies include evaluation of PRRT with alpha radiation emitters such as Actinium-226 in augmenting CART response.

Structural modifications to chelator and linker compositions improved tumor targeting and pharmacokinetics (PK) of Pb peptide-based radiopharmaceuticals for NET theranostics. These findings suggest that PSC-PEG-TOC is a promising candidate for Pb-based targeted radionuclide therapy for NETs and other types of cancers that express SSTR2.

P1/2, N=52, Recruiting, Viewpoint Molecular Targeting | Not yet recruiting --> Recruiting

Our results identify SSTR2 as a promising target for COAD immunotherapy. Our findings provide new insights into the biological functions of the SSTR family and their implications for the prognosis of COAD.

Results will be presented at conferences and submitted to peer-reviewed journals for publication and will be available on ClinicalTrials.gov. EUDRACT number: 2020-003800-15, NCT05178693.

Tumor invasion is negatively correlated with SSTR2 level but is not associated with other SSTR subtypes. Patients with invasive tumors have a poorer response to SSA therapy, which may be due to the low level of SSTR2 expression. Therefore, SSTR2 could be considered as a routine investigative marker for aiding management of postoperative residual tumors.

These findings suggest tumor heterogeneity and lack of genomic aberrations in EBV-associated LECSGs. The heterogenous and unusual immunohistochemical features explain the diagnostic difficulties and simultaneously extend the immunophenotype spectrum of this tumor entity.

Ga-SSO-120 PET offers high diagnostic precision with comparable detection rates and additional complementary information to the gold standard, F-FDG PET. Consistent uptake in most patients warrants exploration of SSTR2-directed radionuclide therapy.

In SSTR2-positive xenograft-bearing mice, the combination of nedisertib (a DNA-PK specific inhibitor) and LuTate produced a more robust control of tumour growth and increased survival compared to LuTate alone. DDR pathways are critical for sensing and repairing radiation-induced DNA damage, and our study shows that regulation of DDR pathways may be involved in both resistance and sensitivity to PRRT. Additionally, the use of a DNA-PK inhibitor in combination with LuTate PRRT significantly improves the efficacy of the treatment in pre-clinical models, providing further evidence for the clinical efficacy of this combination.

Targeting SSTR2 positive meningioma cells with an adaptor FITC CAR T-cell system is feasible. Syngeneic murine models and the use of adaptor molecules directed against murine SSTR2 will be required to explore secondary immune reactions and off-tumor effects prior to proceeding to early phase clinical trials.

In particular, SSTR2 expression is clinically valid because it is associated with metastatic disease at the time of diagnosis and can thus serve as a prognostic marker. Moreover, SSTR2 overexpression provides a molecular basis for tumour imaging and treatment with somatostatin analogues.

Our study is the first to shed light on the intricate relationship between SSTR2 and EGFR in NPC and provides new insights into the potential benefits of EGFR targeted therapy for patients with high SSTR2 expression. Additionally, SSTR2 has potential as a new biomarker for poor prognosis in NPC patients.

Recurrent and metastatic NPC is treated with cisplatin-based chemotherapy regimens, with poor survival...Thus, in SSTR2-H NPC, immunotherapy and also SSTR2-directed strategies may be appropriate therapeutic strategies. In EBV- NPC, PIK3CA-directed therapy merits further investigation.

101 (b), this study was performed utilizing retrospective, deidentified clinical data. Therefore, this study was deemed Institutional Review Board exempt, and no patient consent was necessary from the subjects.

OC patients displayed a significant inverse relationship between SSTR2 and TSHR expression that was not seen in OA patients. This may be a key relationship that can be utilized to prognosticate and treat OCs.

For the first time, we show that this higher tumor uptake results in significant anti-tumor response when compared to standard PRRT alone. These preclinical results provide a rationale for utilizing HDACi pretreatment to improve targeted radionuclide therapy in patients with SSTR2-negative, metastatic PNETs.

Our results suggest that specific red marrow uptake of [Lu]Lu-DOTATATE is in line with observations of somatostatin receptor type 2-expressing hematopoietic progenitor cells within the bone marrow. Blood-based dosimetry methods fail to account for the prolonged elimination of specific uptake and underestimate the absorbed dose to red marrow.