Abstract Library

#4396 Hypoxic microenvironment in neuroendocrine tumours

Introduction: The hypoxic microenvironment is a hallmark of many solid tumours, including neuroendocrine tumours (NETs). Hypoxia plays a crucial role in tumour progression, metastasis, and therapy resistance. However, the specific mechanisms by which hypoxia influences NET behaviour remain poorly understood.

Conference:

Presenting Author:

Authors: Xu L, Yu P, Ye M, Chen J, Tang Q,

Keywords: Neuroendocrine tumour, hypoxia, HIF-1α, VEGF, mTOR, PI3K/AKT, drug resistance, EMT,

#4378 Hypoxic signalling in pancreatic NETs (pNETs)

Introduction: In a genomic profiling study conducted as part of the COMPOSE Phase III multicentre open-labelled clinical trial we assessed 9 pNET patients, 2 of which showed upregulation of CA9 and hypoxic signalling. Hypoxic tumour cells present CA9 for extracellular proton channelling, maintenance of intracellular pH and to acidify and thereby vascularise and immune-suppress the TME. In normoxia, EGLN1-3 hydroxylate proline residues of HIF1A for its subsequent ubiquitination by the VHL-complex resulting in degradation and repression of its target genes.

Conference:

Presenting Author: Walter T

Authors: Walter T, Smutna V, Srirajaskanthan R, Capdevila J, Qin Y,

Keywords: hypoxia, pNET, HIF1A, CA9, Case study, hypoxic, genomic profiling,

#3767 Metabolic alterations in patients with pheochromocytoma/paragangliomas and SDHB mutations

Introduction: Pheochromocytoma/paragangliomas (PPGL) patients with SDHB mutation may have unfavourable course of disease. SDHB gene inactivation results in up-regulation of glycolytic reaction and activation of pseudo-hypoxic phenotype in preclinical studies.

Conference:

Presenting Author: Benevento E

Authors: Benevento E, Cannavale G, Liccardi A, Minotta R, Modica R,

Keywords: pheochromocytoma, paraganglioma, SDHB,

#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,

#3493 Molecular characterization of the splicing machinery in pheochromocytomas and paragangliomas unveils a marked dysregulation with instructive potential

Introduction: Pheochromocytomas and paragangliomas(PPGL) are rare neuroendocrine neoplasms. Up to 25% will develop distant metastases or aggressive behaviour, but there is a lack of accurate risk markers able to stratify patients according to their potential outcome. Genomic characterization of PPGLs has identified 3 clusters: Pseudohypoxic-profile, MAPK-pathway alteration, and Wnt-pathway dysregulation. Alternative splicing dysregulation is emerging as a novel hallmark of cancer, due to its link to oncogenesis and aggressiveness in different neoplasms, including NENs.

Conference:

Presenting Author:

Authors: Moreno-Montilla M, Encinas Rey R, Martínez Montes A, García-Vioque V, Alors-Pérez E,

Keywords: pheochromocytoma, paraganglioma, metastasis, splicing dysregulation, splicing machinery,