Endocrine Abstracts

Background: Targeted therapies for somatostatin receptor-positive NETs have seen significant developments in recent years. Approved and investigational somatostatin analogs for GEP-NETs are changing the treatment landscape for these cancers allowing for better management of difficult-to-treat heterogeneous tumors. To improve competence in applying these advances and to consider patient perspectives in treatment selection, an educational initiative was designed in collaboration...

Background: More than 12,000 people in the United States are diagnosed with a NET each year and approximately 175,000 people are living with this diagnosis. Little progress has been made in the therapy of NETs over the last two decades, and identification of new vulnerabilities remains a priority.Methods: We used two libraries of compounds selected for potential repurposing and identified agents with the highest cytotoxic activity in neuroendocrine model...

Background: There has been increasing interest in the relationship between lifestyle and NET. Results from previously published small observational studies indicate that smoking, alcohol and diabetes may contribute to NET development, but the reported data is conflicting. Additionally, little data is available on diet and physical activity. The aim of the current study is to investigate the association between lifestyle factors and NET development in a large prospective cohort...

Background: Genomic structural variants (SVs) encompass a large portion of mutations driving cancer progression, however, there is a paucity of data regarding such drivers in metastatic neuroendocrine tumor (mNET). Existing studies have focused on short-read sequencing of primary NET samples, which can detect single nucleotide variants, but are unable to identify larger SVs. Such studies have demonstrated a low rate of genetic mutations. Optical genome mapping (OGM) represents...

Background: Appendiceal GCA is a tumor which has been misunderstood for decades. GCAs are comprised of goblet-like mucinous cells, with variable numbers of neuroendocrine and Paneth-like cells and lie on the spectrum between appendiceal adenocarcinoma and neuroendocrine tumors. Prognosis depends on the stage and tumor grade; 30% of patients with low-grade and 50-70% of high grade GCAs present with metastatic disease. Currently, there are limited systemic therapy options and de...

Background: nab-Sirolimus, approved in the US for patients with advanced malignant PEComa, is a novel albumin-bound mTOR inhibitor (mTORi) that inhibits the mTOR pathway via suppression of the mTORC1 complex. When TSC1 or TSC2 is inactivated via mutation or loss, the mTOR pathway may be aberrantly activated. TSC1 and TSC2 alterations occur in a range of common cancers. Clinically, in the AMPECT exploratory analysis of nab-sirolimus in advanced malignant PEComa (NCT02494570), 8...

Background: Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are a clinically heterogenous group. Determining the appropriate selection of therapy and optimal monitoring can be difficult due to their diverse behavior. Furthermore, monitoring or surveillance typically consist of frequent imaging, potentially over decades. Circulating tumor DNA (ctDNA) has shown promise as a minimally invasive approach to disease monitoring and treatment response assessment in a variety o...

Background: Metastatic paragangliomas (PGL) and pheochromocytomas (PCC) are rare neuroendocrine diseases with an incidence of 2 to 8 people per million, a prevalence between 1:2500 and 1:6500 and a strong hereditary disposition. However, due to the rarity of the disease, there is relatively limited data on treatment options, including radionuclide therapy using radioisotope analogs of MIBG and dotatate. There are a few published small series on clinical benefits of treating PG...

Background: Somatostatin analogues (SSAs) are first-line standard of care therapies for gastroenteropancreatic neuroendocrine tumors (GEP-NET), showing efficacy in tumor/symptom control with an established safety profile. Yet, disease progression may occur despite standard-dose SSA treatment, requiring more aggressive and toxic therapies. Retrospective/non-randomized data suggest higher-dose SSAs may benefit patients with GEP-NET who do not respond to standard-dose treatment a...

Background: Paltusotine is an investigational oral, once-daily, small molecule somatostatin receptor type 2 agonist in development for the treatment of acromegaly and carcinoid syndrome associated with neuroendocrine tumors.Methods: This multicenter, open-label, phase 1 study enrolled participants with mild, moderate, and severe hepatic impairment based on Child-Pugh classification and matched healthy participants. A single 20-mg oral dose of paltusotine...