Abstract Library

#4607 BH3-mimetic drugs elicit cell death of neuroendocrine tumours in preclinical models – An emerging therapeutic strategy for NETs

Introduction: There is an unmet clinical need to identify new, effective therapies for patients with neuroendocrine tumours (NETs). Analysis of single-cell expression data revealed that NETs express high levels of the Bcl2 family of antiapoptotic proteins. Therefore, we hypothesised that proapoptotic drugs, such as BH3-mimetics, can induce programmed cell death, i.e., apoptosis, of neuroendocrine cancer cells.

Conference:

Presenting Author: Michael I

Authors: Kulathunga N, Wang Z, Kale J, Lens A, Tsui H,

Keywords: neuroendocrine tumour, BH3-mimetics, Navitoclax, Cabozantinib, patient-derived organoids, apoptosis, 177Lu-Dotatate,

#4588 Spatial transcriptomics identifies Wnt signalling in multifocal ileal neuroendocrine tumours

Introduction: Ileal neuroendocrine tumours (i-NETs) often present with multiple primary tumours (>30-40%). Recent studies showed no shared somatic mutations in multiple primary tumours, highlighting the need to examine the tumour microenvironment in tumorigenesis. The Wnt signalling pathway is crucial for organ stem cell regulation. While the Wnt/β-catenin pathway influences prostate and pancreatic NET/Cs, its role in i-NETs remains unclear.

Conference:

Presenting Author:

Authors: Yogo A, Akanuma N, Kim G, Thirlwell C, Mäkinen N,

Keywords: Wnt Signalling, Spatial Transcriptomics,

#4539 Single-nucleus profiling of the tumour microenvironment in SI-NET patients

Introduction: Small intestinal neuroendocrine tumours (SI-NETs) are frequently present as multiple synchronous primary tumours in the small bowel. They are thought to arise from enterochromaffin (EC) cells in the gut, which account for less than 1% of the intestinal epithelium. Previously reported lack of shared somatic driver alterations in SI-NETs suggests that other, non-genetic mechanisms are likely involved in their tumorigenesis.

Conference:

Presenting Author: Mäkinen N

Authors: Mäkinen N, Kasai Y, Kim G, Thirlwell C, Nakakura E,

Keywords: small intestinal NET, tumour microenvironment, single-nucleus sequencing,

#4446 Uncommon ophthalmic presentation of a small bowel neuroendocrine tumour: Case report

Introduction: Neuroendocrine tumours (NETs), including carcinoid tumours, are slow-growing neoplasms commonly originating in the gastrointestinal tract or bronchus, but they can also arise in other sites. Due to their indolent nature, the majority of NETs are diagnosed at an advanced stage, typically to the lymph nodes, liver, or bones.

Conference:

Presenting Author:

Authors: Hamidatou K, Behourah Z, Ahed Messaoud M, Megaiz A, Lechar M,

Keywords: Neuroendocrine tumour, Carcinoid tumour, Orbital metastasis, somatostatin analogue injection,

#4373 Focal adhesion kinase drives proliferation and invasion in gastrointestinal neuroendocrine tumours via modulation of transformative cell signalling and gene expression

Introduction: Focal Adhesion Kinase (FAK) is a non-receptor protein kinase that localises in both the cytoplasm and nucleus, influencing cell function through its enzymatic and scaffold activities. Through its scaffold function, FAK modulates gene expression epigenetically. Gastrointestinal neuroendocrine tumours (GI-NETs) exhibit a relatively low mutation rate, supporting the hypothesis that these malignancies may be driven epigenetically. Recently, PROTAC (PROteolysis TArgeting Chimeras) technology has enabled selective inhibition and degradation of FAK, providing a novel approach to explore its role in GI-NETs.

Conference:

Presenting Author: Gagliano T

Authors: Toffoli L, Ditsiou A, Moschioni E, Hamm V, Gagliano T,

Keywords: FAK, GI-NET, Cell Signalling, Epigenetics,