Endocrine Abstracts

Background: Neuroendocrine tumor (NET) patients with diminished SSTR2 expre-ssion are not eligible for any type of SSTR2-specific imaging or treatment. Herein, we propose to epigenetically enhance and enable somatostatin receptor type 2 (SSTR2)-targeted theranostics for patients with NETs. Specifically, we have found that simultaneous inhibition of DNA methylation and his-tone de-ace-tylation enhanced SSTR2 expression and in vitro binding of [68Ga]DOTATATE....

Background: The 5-year survival rate for patients with unresectable, metastatic pancreatic neuroendocrine tumors (pNETs) remains less than 30%, emphasizing the need for new and effective treatment options for patients with advanced pNETs. Notch1 signaling is a critical cell-cell communication pathway responsible for regulating differentiation, cell fate determination, and epithelial-mesenchymal transition (EMT). Notch1 plays a critical role in the differentiation state of NE c...

Background: There are known outcome disparities between Black and White patients with pancreatic neuroendocrine tumors (pNETs). Recently, Black patients were shown to have higher rates of lymph node metastasis in smaller tumors than White patients, indicating possible differences in tumor biology. Numerous prognostic gene expression differences between racial groups have been reported in other cancers, but no such analysis has been conducted in pNETs. This study evaluated pNET...

Background: The 5-year survival rate for patients with advanced pancreatic neuroendocrine tumors (pNETs) is less than 30%. Notch signaling is a transmembrane receptor pathway with four distinct isoforms, activation of which is linked to cellular differentiation, cell fate, and viability. Both Notch1 and Notch3 signaling have been shown to be dysregulated in pNETs. Notch3 activation has been shown to repress Notch1 activity in other cancers. We hypothesize that activation of No...

Background: Patients with neuroendocrine tumors (NETs) have a 5-year survival rate of 30-60%. Surgery, and newly approved ‘tar-geted radionuclide therapy (TRT)’ with [177Lu]DOTATATE, are the only curative options for patients with NETs. TRT is limited to pa--tients that have high levels of somatostatin receptor subtype 2 (SSTR2) and can im-prove the survival of patients with low-grade tumors, but has little effect on high-grade NETs that express low SSTR2 ...

Background: Various social determinant of health (SDOH) metrics and indices are utilized to evaluate access to cancer care and to explain disparities in outcome in pancreatic neuroendocrine tumors (PNETs). Little prior work has compared the validity of various geographic metrics. Therefore we aimed to examine different geographic metrics validity (from smallest to largest: census block group< census tract< zip code< county) utilizing single institutional data in a ...

Background: Tumor size and lymph node involvement (stage) have been utilized to prognosticate pancreatic neuroendocrine tumors (PNETs) but the influence of race and social vulnerability on these factors remains unexplored. Therefore we sought to explore this in a racially and socioeconomically diverse cohort.Methods: We reviewed records of all patients who underwent surgical resection for PNETs from 2006-2022 at a single NCI-designated cancer center in t...

Background: Current theragnostic techniques for pancreatic neuroendocrine tumors (pNETs) exploit the overexpression of somatostatin receptors (SSTRs) on the cell surface. However, approximately 25% of low-grade and most high-grade pNETs do not express SSTRs, requiring alternative theranostics. Calreticulin (CALR) is a protein linked to reticular calcium homeostasis and immunogenic cell death. Upon sufficient cellular insult, CALR translocates from the endoplasmic reticulum (ER...

Background: Cancer cells utilize both oxidative phosphorylation (OXPHOS) and glycolysis to generate energy. Switching between OXPHOS and glycolysis can promote tumor progression. The mechanisms governing oncogenic metabolic flexibility are largely unknown, but recent data has suggested that Notch1 dysregulation in cancer cells can contribute to altered metabolic phenotypes. We hypothesized that Notch1 signaling supports metabolic flexibility in pancreatic neuroendocrine tumor ...

Background: Following IHC of CALR, H-scoring was performed by a pathologist. H-scoring was validated by MIF of the same tissue, wherein random-forest machine learning (ML) classifiers were employed to classify cells. ML classifiers were trained to distinguish between pNET cells and tumor stroma using approximately 30% of cells for the respective cell population of interest in each TMA core. Pearson’s correlations were used to evaluate the relationship between H-scoring an...