Tackling drug activity and resistance mechanisms in neuroendocrine tumors treated with cabozantinib

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Introduction: Neuroendocrine tumors (NETs) are highly vascularized malignancies and angiogenesis plays a relevant role in cell proliferation and survival. Nowadays, innovative therapies have amplified the paradigm treatment of NETs. Among the compounds with anti-vascular properties, cabozantinib (CAB) appeared promising.

Aim(s): The aim of this study is to investigate the activity of CAB in different NETs models.

Materials and methods: We analysed the anti-tumor activity of CAB against NETs utilizing in vitro and in vivo models. For cell cultures we used BON-1, QGP-1, NCI-H727 and NCI-H720 cell lines. Cell viability was assessed by manual count coupled with quantification of cell death, performed through FACS analysis as propidium iodide exclusion assay. In addition, we investigated the modulation of the anti-apoptotic Myeloid cell leukemia-1 protein under CAB exposure, as putative adaptive pro-survival mechanism, and compared the responses with sunitinib. The activity of CAB was also tested in mouse and zebrafish xenograft tumor models.

Conference:

Presenting Author: Cella C

Authors: Cella C, Cazzoli R, Fazio N, de Petro G, Gaudenzi G,

Keywords: Neuroendocrine tumor, angiogenesis, zebrafish model, mouse model.,