Endocrine Abstracts

Background: Oncolytic viruses (OV) hold potential for not only delivering durable anti-tumor responses but also converting immunologically “cold” tumors to “hot” tumors. Seneca Valley Virus (SVV-001) is a naturally occurring oncolytic picornavirus found to have selectivity for tumor cells with neuroendocrine (NE) properties. Because of the paucity of syngeneic murine NE tumor models, we evaluated the efficacy of Seneca Valley Virus (SVV), in combination wit...

Background: Somatostatin receptor (SSTR) expression has been characterized in well-differentiated neuroendocrine tumors (NET). However, the understanding of receptor expression in various non-neuroendocrine solid tumors is limited. This study was performed to evaluate SSTR-2 in various cancers to provide a rational basis for SSTR-2 targeted anti-cancer therapies.Methods: Formalin-fixed paraffin, paraffin-embedded tissue was obtained from pathology archiv...

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: Peptide receptor radionuclide therapy (PRRT) with Lutetium-177 DOTATATE (LUTATHERA) is an effective treatment option for somatostatin receptor (SSTR) positive metastatic gastroenteropancreatic neuroendocrine tumors (NETs) and has also demonstrated antitumor activity in SSTR positive NETs from other primary sites. While the median progression free survival (mPFS) is around 29 months, there is a subset of patients who are refractory to PRRT and demonstrate progressio...

Background: Chromogranin A (CGA) and 5-HIAA are meaningful biomarkers in managing neuroendocrine tumors (NETs). CGA, though nonspecific, can reflect disease bulk and typically decreases after debulking surgery. 5-HIAA is specific to NETs though its measurement may require a special diet, a 24-hour urine collection, or specialized blood collection tubes; but usually decreases after debulking procedures. Serotonin, though useful in diagnosing NETs, is not followed as a biomarker...

Background: 177Lu-DOTATATE is an FDA and Health Canada-approved treatment option for metastatic, progressive GEPNET patients. 177Lu-DOTATATE is now often considered the treatment of choice for small bowel/midgut patients who have progressed on somatostatin analogs (SSA). Despite 177Lu- DOTATATE’s impressive disease stabilization, many patients will eventually progress. Progression after prior use of PRRT does not necessarily render these tumors resistant to future PRRT tr...

Background: Significant advances have been made in the treatment of gastrointestinal (GI-) and pancreatic (P-) NENs. However, the use of immunotherapy is still limited, with most tumors considered immune “cold”. The cGAS-STING signaling pathway has emerged as a critical mediator of inflammation and immune-mediated responses, with pathway agonists under development for enhancing immunotherapy. In this study, we evaluated associations between cGAS-STING pathway activit...

Background: Immune checkpoint inhibitor (ICI) maintenance therapy is the standard of care for frontline management of extensive-stage small cell lung cancer (ES SCLC). However, the overall survival benefit of the addition of ICI maintenance to frontline ES SCLC treatment is modest and further improvement is needed. We hypothesized that the addition of poly (ADP-ribose) polymerase inhibition to ICI maintenance therapy for patients with platinum-sensitive ES SCLC could improve t...

Background: Radiation is a potent inducer of DNA double-strand breaks, and ribonucleotide reductase (RNR) is the rate-limiting enzyme in the synthesis and repair of DNA, making RNR-targeted therapy a rationale therapeutic strategy for radiosensitization. ETCTN 10388 (NCT04234568) evaluated safety and efficacy of the combination of lutetium 177 DOTATATE, a beta-emitting radionuclide in combination with triapine, a ribonucleotide reductase (RNR) inhibitor. <p class="abstext"...

Background: Radiolabeled somatostatin analogs provide a means of delivering targeted radiation with a high therapeutic index to NETs that express somatostatin receptors (SSTRs). We hypothesize that the addition of an effective radiation sensitizer could help improve the antitumor activity of Lutathera. Radiation is a potent inducer of DNA damage. The primary repair mechanism of radiation-induced double-stranded breaks (DSBs) is the nonhomologous end-joining (NHEJ) pathway, in ...