Endocrine Abstracts

Background: BCL-2 is an anti-apoptotic protein associated with resistance to tumor cell death and is a histopathologic marker of neuroendocrine differentiation. We characterized the transcriptomic profile of BCL2 expression in NENs and its association with site, immune infiltration, and overall survival (OS).Methods: Next-generation sequencing of both DNA (592-gene panel or whole exome) and RNA (whole transcriptome) was performed on NENs of pancreatic (P...

Background: SSTR substypes are collectively expressed in the majority of NENs. However, SSTR subtype expression is not routinely assessed for clinical decision-making, including patients eligible for targeted radionucleotide therapy. Elucidating the landscape of SSTR subtypes in context of molecular profiles for low-grade (LG-) and high-grade NENs (HG-NENs) provides an opportunity to better tailor targeted therapy. Here, we leverage the ability of transcriptomics to predict NE...

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: 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: 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 ...