Abstract Library

#3848 LITESPARK-015 cohort B1 – A phase 2 open-label study of Belzutifan (a HIF-2α inhibitor) monotherapy in patients with von Hippel-Lindau (VHL) disease–associated tumors

Introduction: Patients (pts) with von Hippel-Lindau (VHL) disease need novel targeted therapies. Hypoxia-inducible factor 2α (HIF-2α) is a key oncogenic driver in VHL disease. Belzutifan (MK-6482), a HIF-2α inhibitor, has shown antitumor activity in pts with advanced renal cell carcinoma (RCC) and pancreatic neuroendocrine tumors (pNETs); more data are needed in VHL disease–associated localized tumors.

Conference:

Presenting Author:

Authors: Walter T, Gong K, Nakamura E, Iliopoulos O, Jimenez C,

Keywords: von Hippel-Lindau disease, belzutifan, MK-6482,

#3796 The effect of pseudohypoxia on the immune microenvironment of pancreatic neuroendocrine neoplasms (PanNEN)

Introduction: Pancreatic neuroendocrine tumors may develop sporadically or as part of an inherited disease, such as von Hippel-Lindau (VHL). VHL disease is caused by a germline pathogenic variant in the VHL gene encoding VHL protein (pVHL). Hypoxia inducible factor (HIF) is responsible for cellular oxygen supply. Its degradation is mediated in normoxic states via ubiquitination and inhibited by pVHL. Hence, pVHL deficiency leads to pseudohypoxia due to HIF overexpression. Several studies suggested immunomodulatory role for HIF in kidney cancer.

Conference:

Presenting Author:

Authors: Solomon Chmelnik A, Telerman A, Tirosh A,

Keywords: Pancreatic neuroendocrine tumor, VHL, DNA methylation, Immune cells, PD-L1,

#3790 Pancreatic neuroendocrine tumors (pNETs) in French VHL mutation carriers – A nationwide retrospective study with genotype-phenotype correlations

Introduction: Von Hippel-Lindau disease (VHL) is a rare inheritable syndrome predisposing to pancreatic neuroendocrine tumors (pNETs). The natural history of VHL-related pNETs is ill-known.

Conference:

Presenting Author:

Authors: Muller M, Hammel P, Sauvanet A, Couvelard A, Vullierme M,

Keywords: hereditary neoplastic syndrome, von Hippel-Lindau disease, VHL gene, pancreatic neuroendocrine tumor,

#3748 Association of MINEN with GIST on neurofibromatosis – A case report

Introduction: Although most digestive neuroendocrine tumors (NETs) are sporadic, around 5% of NETs occur in a context of hereditary predisposition, mainly type 1 multiple endocrine neoplasia (NEM1) and Von Hippel-Lindau disease (VHL).

Conference:

Presenting Author:

Authors: Samia K, Fatima H, Nabil B, Benali T, Aisha B,

Keywords: NEN, GIST, MINEN, DOG1,

#3688 Novel von Hippel-Lindau-related pancreatic neuroendocrine neoplasms in-vivo model

Introduction: Von Hippel-Lindau (VHL) disease is a familial cancer syndrome caused by a germline mutation in the VHL tumor suppressor gene. Although VHL-related pancreatic neuroendocrine neoplasms (vPNEN) have been reported, their molecular pathogenesis is not fully investigated.

Conference:

Presenting Author:

Authors: Telerman A, Yossef Y, Chmelnik A, Tirosh A,

Keywords: VHL, PNEN, BON1, pseudohypoxia, CDX,