Comparison of drug sensitivity profiles of various NEN spheroids

#3536

Introduction: Neuroendocrine neoplasms (NENs) are rare cancers that arise from neuroendocrine cells. NENs are classified as well-differentiated neuroendocrine tumors (NETs) and poorly differentiated neuroendocrine carcinomas (NECs). Small bowel and pancreatic NETs (SBNET & PNETs) are generally slow-growing but commonly metastasize to the liver and become aggressive cancers. Little is known about the drug sensitivity profile of these 3 NENs due to the lack of cellular and animal models of these malignancies. Recently, we have developed a protocol to culture NEN cells from patient tumors as patient-derived spheroids (PDS) and showed expression of NEN markers. The rarity and slow growing features of these spheroids have been hindering drug screens with many compounds.

Aim(s): We aim to systematically test NEN spheroids against a library of 175 compounds and compare their drug sensitivity profiles to identify specific classes of inhibitors for each NEN group.

Materials and methods: We used 20 NEN PDS cultures (11 SBNETs, 6 PNETs, and 3 NECs) to screen against a panel of 175 compounds. NEN spheroid viability was quantified. The activity of the top 2 drugs was tested in a new NEC mouse model.

Conference:

Presenting Author: Ear P

Authors: Tran C, Luis B, Sherman S, Mudd J, Abusada E,

Keywords: NET, NEC, spheroid, drug screening, PDX model,