EZH2 Inhibition as New Epigenetic Treatment Option for Pancreatic Neuroendocrine Neoplasms (PanNENs).

Cancers
Simon Leonhard April-MonnIlaria Marinoni

Abstract

Pancreatic neuroendocrine neoplasms are epigenetically driven tumors, but therapies against underlying epigenetic drivers are currently not available in the clinical practice. We aimed to investigate EZH2 (Enhancer of Zest homolog) expression in PanNEN and the impact of EZH2 inhibition in three different PanNEN preclinical models. EZH2 expression in PanNEN patient samples (n = 172) was assessed by immunohistochemistry and correlated with clinico-pathological data. Viability of PanNEN cell lines treated with EZH2 inhibitor (GSK126) was determined in vitro. Lentiviral transduction of shRNA targeting EZH2 was performed in QGP1 cells, and cell proliferation was measured. Rip1TAG2 mice underwent GSK126 treatment for three weeks starting from week 10 of age. Primary cells isolated from PanNEN patients (n = 6) were cultivated in 3D as islet-like tumoroids and monitored for 10 consecutive days upon GSK126 treatment. Viability was measured continuously for the whole duration of the treatment. We found that high EZH2 expression correlated with higher tumor grade (p < 0.001), presence of distant metastases (p < 0.001), and shorter disease-free survival (p < 0.001) in PanNEN patients. Inhibition of EZH2 in vitro in PanNEN cell lines and in...Continue Reading

Related Concepts

Related Feeds

Adenoma, Islet Cell

Islet Cell Adenoma arises in the islet cells, which are insulin producing cells of the pancreas. These tumors can be either malignant or benign. Discover the latest research on Islet Cell Adenoma here.

Carcinoma, Islet Cell (Keystone)

Islet Cell Carcinoma or Pancreatic Neuroendocrine Tumours arise in the hormone producing cells of the pancreas. These tumors can be either malignant or benign. Discover the latest research on islet cell carcinoma in this feed.

Cell Signaling & Cancer Epigenetics (Keystone)

Epigenetic changes are present and dysregulated in many cancers, including DNA methylation, non-coding RNA segments and post-translational protein modifications. This feed covers the latest research on signaling and epigenetics in cell growth and cancer.

Carcinoma, Islet Cell

Islet Cell Carcinoma or Pancreatic Neuroendocrine Tumours arises in the hormone producing cells of the pancreas. These tumors can be either malignant or benign. Discover the latest research on Islet Cell Carcinoma here.