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

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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.

Aim(s): This study aims to assess the effectiveness of BH3-mimetics alone or combined with standard-of-care (SOC).

Materials and methods: NET patient-derived organoids (PDOs) were established from fresh surgical surplus NET tissue samples and treated with combinations of BH3-mimetics and SOC (Sunitinib, Cabozantinib, Everolimus, and 177Lu-Dotatate). Their responses were monitored using non-toxic dyes and confocal imaging.

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,