Cannabis and endocannabinoid system modulation as novel strategies to improve conventional treatment outcomes and overcome drug resistance in neuroendocrine neoplasms in-vitro & in-vivo models

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Introduction: NENs are treated with systemic therapies with limited non-curable efficacy due to development of drug resistance (DR). While cannabis and its extracts (cannabinoids, CE) are mostly used for their palliation properties, increasing evidence suggests an anticancer trait via several cellular pathways. Limited data exist on cannabis and the endocannabinoid system (ECS) in NENs and their impact on the development of DR.

Aim(s): To understand the anti-tumor role of cannabinoids and the ECS in NENs, as well as ECS manipulation to overcome resistance to conventional NEN therapy.

Materials and methods: Endocannabinoid receptors (ECR) expression on NENs cell lines and human tumor samples was profiled using FACS/IF staining and RNA-Seq. NENs cells were treated with multiple CE; cell viability & apoptosis were tested using WST-1 and Annexin/PI staining. Cell cycle was examined with PI staining/CFSE labelling. ECR blocking was used to examine their role in cell death. In vivo anti-tumor effect was tested by combining Everolimus (EVE) with CE/ECR-antagonists in a NENs mice model.

Conference:

Presenting Author: Avniel-Polak S

Authors: Avniel- Polak S, Polak D, Drier Y, Grozinsky-Glasberg S,

Keywords: neuroendocrine neoplasm, cannabinoids, cannabis extracts, endocannabinoid system, endocannabinoid receptors, everolimus,