Endocrine Abstracts

Background: Advanced small cell lung cancer (SCLC), extra-pulmonary neuroendocrine carcinoma (EP-NEC) and pancreatic adenocarcinoma (PDA) are rapidly progressive cancers characterized by unbridled replication stress. Patients with these malignancies possess dismal prognoses with limited options after initial first-line chemotherapy. These tumors rely on the integrity of DNA damage repair pathways to ensure genomic stability. The ataxia telangiectasia and Rad3-related (ATR) pro...

Background: Gastroenteropancreatic neuroendocrine tumors (GEP-NETs), which frequently develop metastatic disease, represent an estimated 70% of NETs. There are limited treatment options with current standard therapies for well-differentiated aggressive grade 2 and grade 3 (Ki-67 index 15−55%) GEP-NETs; however, these may include somatostatin analogues; peptide receptor radionuclide therapy (PRRT); molecular targeted therapies (everolimus or sunitinib); chemotherapy; and ...

Background: Neuroendocrine tumors (NETs) are classified as functional or non-functional based on the presence of characteristic symptoms, related to tumoral secretion of biologically active peptides or amines. Carcinoid Syndrome (CS) is the commonest functional NET syndrome, seen at diagnosis in 19% of patients. It is characterized in over 80% of cases by watery diarrhea (mainly due to serotonin hypersecretion) or cutaneous flushing. Somatostatin is a neuropeptide that inhibit...

Background: Poorly differentiated neuroendocrine carcinoma (NEC) is an aggressive malignancy comprising both pulmonary and extrapulmonary primary sites. NEC includes both small cell lung cancer (SCLC) and large cell neuroendocrine carcinoma (LCNEC), as well as other neuroendocrine carcinomas arising from any primary organ. The optimal systemic therapy beyond first line platinum and etoposide is not established. There is a critical need to improve upon the median survival in th...

Background: Patients with advanced pheochromocytoma/paraganglioma (PPGL) or pancreatic neuroendocrine tumor (panNET) are in need of novel targeted therapies. Hypoxia-inducible factor 2α (HIF-2α) is one of the key oncogenic drivers in neuroendocrine tumors. Hypoxia signaling pathway alterations or other mechanisms that stabilize HIFs are common in some PPGLs and panNETs. Belzutifan (MK-6482), a HIF-2α inhibitor, has shown antitumor activity in advanced renal cell...

Background: Well-differentiated gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are commonly characterized by overexpression of somatostatin receptor subtype 2 (SSTR2), which can be targeted by radiopharmaceutical therapy (RPT) via radiolabeled somatostatin analogues (SSAs). RYZ101 (Ac-225 DOTATATE) is a first-in-class, highly potent alpha-emitting RPT being developed for the treatment of SSTR2+ solid tumors. Alpha-particles (such as emitted by Actinium-225) have a sho...

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: GEP-NETS and PPGLs in pediatric patients are rare; however, recognition of these diseases has increased recently. 10–20% of pediatric patients with GEP-NETs and up to 47% of pediatric patients with PPGLs present with metastatic disease at diagnosis. The disease is often unresectable with poor prognosis, and very few non-surgical therapies are approved for these patients. Due to paucity of data surrounding treatments for pediatric patients with advanced GEP-NET...

Background: Well-differentiated GEP NETs show positive uptake on Ga-68-DOTATOC PET/CT, a somatostatin-receptor (SSTR)-specific imaging tracer. 18F-FDG PET/CT is preferred for aggressive, high-grade NETs as GLUT (glucose-transporter) receptor expression entails poorer prognosis. Grade 2 NET may demonstrate heterogenous uptake of both tracers; suggestive of tumor heterogeneity. PRRT is widely available at reasonable cost since Lu-177-DOTATATE is manufactured indegenously, and is...

Background: TQ Formula (TQ, C10H12O2), is an oral formulation, derived from the black seed (Nigella sativa, Ranunculaceae family), and has anti-oxidant, anti-angiogenic effects. TQ Formula has been shown to induce significant immune modulatory effects in a recently published Covid-19 study. Previous studies reported blackseed’s apoptotic and anti-proliferative effects of its components on multiple cancer types, including colon, breast and ovarian adenocarcinoma. Our preli...