PUBLICATION
Cabozantinib in neuroendocrine tumors: tackling drug activity and resistance mechanisms
- Authors
- Cella, C.A., Cazzoli, R., Fazio, N., De Petro, G., Gaudenzi, G., Carra, S., Romanenghi, M., Spada, F., Grossi, I., Pallavicini, I., Minucci, S., Vitale, G.
- ID
- ZDB-PUB-231020-50
- Date
- 2023
- Source
- Endocrine-related cancer 30(12): (Journal)
- Registered Authors
- Keywords
- cancer, molecular biology, mouse models, tumor angiogenesis, zebrafish model
- MeSH Terms
-
- Neuroendocrine Tumors*/pathology
- Animals
- Mice
- Signal Transduction
- Cell Line, Tumor
- Humans
- Zebrafish*
- PubMed
- 37855330 Full text @ Endocr. Relat. Cancer
Citation
Cella, C.A., Cazzoli, R., Fazio, N., De Petro, G., Gaudenzi, G., Carra, S., Romanenghi, M., Spada, F., Grossi, I., Pallavicini, I., Minucci, S., Vitale, G. (2023) Cabozantinib in neuroendocrine tumors: tackling drug activity and resistance mechanisms. Endocrine-related cancer. 30(12):.
Abstract
Neuroendocrine tumors (NETs) are highly vascularized malignancies in which angiogenesis may entail cell proliferation and survival. Among the emerging compounds with antivascular properties, cabozantinib (CAB) appeared promising. We analyzed the antitumor activity of CAB against NETs utilizing in vitro and in vivo models. For cell cultures, we used BON-1, NCI-H727 and NCI-H720 cell lines. Cell viability was assessed by manual count coupled with quantification of cell death, performed through fluorescence-activated cell sorting analysis as propidium iodide exclusion assay. In addition, we investigated the modulation of the antiapoptotic myeloid cell leukemia 1 protein under CAB exposure, as a 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. Cabozantinib showed a dose-dependent and time-dependent effect on cell viability and proliferation in human NET cultures, besides a halting of cell cycle progression for endoduplication, never reported for other tyrosine kinase inhibitors. In a transplantable zebrafish model, CAB drastically inhibited NET-induced angiogenesis and migration of implanted cells through the embryo body. CAB showed encouraging activity in NETs, both in vitro and in vivo models. On this basis, we envisage future research to further investigate along these promising lines.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping