Searchable abstracts of presentations at key conferences in endocrinology

ea0098b21 | Basic Science | NANETS2023

Transcriptomic profiling of the BCL-2 pathway in Neuroendocrine Neoplasms (NENs)

Sukrithan Vineeth , Ahmed Uzair , Krause Harris , Gandhi Nishant , Walker Phillip , Lou Emil , Soares Heloisa , Vanderwalde Ari , Konda Bhavana

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...

ea0089o9 | Other | NANETS2022

Leveraging Transcriptomics to Grade Pancreatic Neuroendocrine Neoplasms(NENs) and Assess Molecular Alterations Associated with Somatostatin Receptor(SSTR) Subtype Expression

Lou Emil , Gandhi Nishant , Farrell Alex , Xiu Joanne , Seeber Andreas , Shaalan Beg Muhammad , Darabi Sourat , J. Demeure Michael , Abraham Jim , Oberley Matthew , Marshall John , Soares Heloisa

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...

ea0098b25 | Basic Science | NANETS2023

A STING Operation in neuroendocrine neoplasms

Eagal Erika , Lou Emil , Gandhi Nishant , Elliott Andrew , Sukrithan Vineeth , Vijayvergia Namrata , Puri Sonam , Chauhan Aman , Hadfield Matthew , Florou Vaia , Affolter Kajsa , Vanderwalde Ari , Soares Heloisa P.

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...

ea0089t6 | Trials In Progress | NANETS2022

ACTION-1: A Randomized Phase Ib/3 trial of RYZ101 Compared with SoC in SSTR2+ Well-Differentiated GEP-NET with Progression Following Lu-177 SSA

Hope Thomas , Mehr Samuel , Morris Michael , Li Daneng , Halperin, MD Daniel , Strosberg Jonathan , Soares Heloisa , Jacene Heather , Pavel Marianne , L. Kunz Pamela , Ferreira Denis , Li Joanne , Ma Kimberly , Rearden Jessica , Moran Susan , Singh Simron

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...

ea0098c27 | Clinical – Nuclear Medicine/Interventional Radiology/Imaging | NANETS2023

ETCTN 10388: A first in human Phase I Trial of Triapine and Lutetium Lu 177 DOTATATE in Well-Differentiated Somatostatin Receptor-Positive Gastroenteropancreatic Neuroendocrine Tumors (GEP-NETs)

Chauhan Aman , Arnold Susanne , Kolesar Jill , Carson William , Weiss Heidi , Yan Donglin , El Khouli Riham , Khurana Aman , Beumer Jan , Soares Heloisa , Mulcahy Mary , Halfdanarson Thorvardur , Li Daneng , Jacene Heather , Ivy Percy , Kohn Elise , Wright John , Rubinstein Larry , Kunos Charles , Anthony Lowell , Konda Bhavana

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"...

ea0098c28 | Clinical – Nuclear Medicine/Interventional Radiology/Imaging | NANETS2023

ETCTN 10450: A phase I trial of peposertib and lutetium 177 DOTATATE in well-differentiated somatostatin receptor-positive gastroenteropancreatic neuroendocrine tumors (GEP-NETs).

Chauhan Aman , Kolesar Jill , Yan Donglin , Li Daneng , Khurana Aman , Edgar Carson William , Arnold Susanne M. , Gore Steven , Rubinstein Larry , Kohn Elise C. , Percy Ivy S. , Xiao Ying , Dewaraja Yuni , Soares Heloisa P. , Hendrik Beumer Jan , Konda Bhavana , Sukrithan Vineeth , Brian Anthony Lowell

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 ...