Targeting dopamine receptor d2 by imipridone suppresses uterine serous cancer malignant phenotype

Wen Hu, Li Zhang, Sammy Ferri-Borgogno, Suet Ying Kwan, Kelsey E. Lewis, Han T. Cun, Tsz Lun Yeung, Pamela T. Soliman, Rohinton S. Tarapore, Joshua E. Allen, Xinyuan Guan, Karen H. Lu, Samuel C. Mok, Chi Lam Au-Yeung

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

Uterine serous cancer (USC) is an aggressive subtype of endometrial cancer, with poor survival and high recurrence rates. The development of novel and effective therapies specific to USC would aid in its management. However, few studies have focused solely on this rare subtype. The current study demonstrated that the orally bioavailable, investigational new drug and novel imipridone ONC206 suppressed USC cell proliferation and induced apoptosis both in vitro and in vivo. Disruption of the DRD2-mediated p38MAPK/ERK/PGC-1α network by ONC206 led to metabolic reprogramming and suppression of both glycolysis and oxidative phosphorylation. ONC206 also synergized with paclitaxel in reducing USC cell viability. In addition, DRD2 overexpression correlated with poor overall survival in patients. This study provides the first evidence that ONC206 induced metabolic reprogramming in USC cells and is a promising therapeutic agent for USC treatment. These findings support further development of ONC206 as a promising therapeutic agent and improves survival rates in patients with USC.

Original languageEnglish (US)
Article number2436
Pages (from-to)1-17
Number of pages17
JournalCancers
Volume12
Issue number9
DOIs
StatePublished - Sep 2020

Keywords

  • Dopamine receptor D2
  • Imipridone
  • Metabolic reprogramming
  • Uterine serous cancer

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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