The CDK4/6 Inhibitor Palbociclib Induces Anti-proliferative Mechanisms in Gastroenteropancreatic Neuroendocrine Neoplasms In Vitro

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Introduction: Gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) are rare tumors with heterogeneous molecular backgrounds and mostly unknown druggable driver mutations. Especially for the midgut NENs effective treatment options are limited. The retinoblastoma pathway is often inactive due to CDK4/6 overexpression in pancreatic NENs. Palbociclib is a FDA approved (ER-positive and HER2-negative breast cancer) cyclin-dependent kinases 4 and 6 inhibitor and might impair cell cycle progression and proliferation.

Aim(s): The molecular and cell biological mechanisms of palbociclib were analyzed to assess the anti-proliferative therapeutic potential in GEP-NENs in vitro.

Materials and methods: GEP-NEN cell lines of pancreatic and gastrointestinal offspring (BON, QGP-1, KRJ-I, LCC-18) were treated with palbociclib (kindly provided by Pfizer Inc.) and analyzed by western blotting, flow cytometry and proliferation assay.

Conference: 13th Annual ENETSConcerence (2016)

Presenting Author: Briest F

Authors: Briest F, Grass I, Siegmund B, Grabowski P,

Keywords: GEP-NEN, targeted therapy, cyclin-dependent kinases 4/6,