SSTR2 expression

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.

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.

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.

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.

The anti-tumor effect was further enhanced when RYZ101 was combined with carboplatin and etoposide at clinically relevant doses. In summary, RYZ101 is a highly potent, alpha-emitting radiopharmaceutical agent, and preclinical data demonstrate the potential of RYZ101 for the treatment of patients with SSTR-positive cancers.

This result demonstrates consistent and strong expression of SSTR2 in PAs as compared to Warthin tumors, which may allow physicians to utilize radioligand-somatostatin analog PET CT/MR imaging to diagnose the PA. SSTR2 positivity, if shown to be clinically relevant, may allow peptide receptor radionuclide therapy in the future.

The median H-score for EBVNPC was 180 (range 12-295; mean 179), whereas the median H-scores for HPVSCC and VNSCC were 0 (range 0-56; mean 8) and 0 (range 0-125; mean 31), respectively (p<0.001 for EBVNPC compared to either). Conclusion Our study validates the strong correlation between SSTR2 immunohistochemistry and EBV status in NPCs, supports its use in clinical practice as a highly sensitive and specific surrogate biomarker, and lends credence to exploring SSTR2-targeted imaging and therapy.

Synthetic therapeutic agonists showing selectivity for SSTR2 (Octreotide) or for SSTR2 and SSTR5 (Pasireotide) have been approved for the treatment of patients with acromegaly and Cushing's syndrome, as their pituitary tumors highly express SSTR2 or SSTR2/SSTR5, respectively...Furthermore, ITF2984 displays antitumor activity that is dependent on SSTR3 expression levels in the MENX (homozygous mutant) NFPA rat model, which closely recapitulates human disease. Therefore, ITF2984 may represent a novel therapeutic option for patients affected by NFPA.

We analyzed effects of combining PRRT and DNA-PKcs inhibitor AZD7648 on viability, cell death and clonogenic survival on SSTR2-expressing cell lines BON1-SSTR2, GOT1 and NCI-H69... These results highlight that the potentiation of the therapeutic effect of PRRT by DNA-PKcs inhibition is a highly effective and well-tolerated therapeutic strategy. Based on our findings, we recommend initiation of phase I/II studies in patients to find a safe and effective combination regimen.

P2, N=52, Recruiting, University of Chicago | Not yet recruiting --> Recruiting

Taken together, this study identifies for the first time a mechanism that targets Sstr2 for lysosomal degradation that is independent of Sstr2 agonist and can be potentiated by Wnt ligand. Intervention in this signaling mechanism has the potential to elevate Sstr2 expression in neuroendocrine tumors and enhance Sstr2-directed therapies.

These results indicate that DNA methylation might be involved in regulating SST expression. However, the role of histone modifications in SI-NETs remains elusive.