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

doi:10.3390/cancers12092436

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 journal › Article › peer-review

8 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 language	English (US)
Article number	2436
Pages (from-to)	1-17
Number of pages	17
Journal	Cancers
Volume	12
Issue number	9
DOIs	https://doi.org/10.3390/cancers12092436
State	Published - Sep 2020
Externally published	Yes

Keywords

Dopamine receptor D2
Imipridone
Metabolic reprogramming
Uterine serous cancer

ASJC Scopus subject areas

Oncology
Cancer Research

Access to Document

10.3390/cancers12092436

Cite this

Hu, W., Zhang, L., Ferri-Borgogno, S., Kwan, S. Y., Lewis, K. E., Cun, H. T., Yeung, T. L., Soliman, P. T., Tarapore, R. S., Allen, J. E., Guan, X., Lu, K. H., Mok, S. C., & Au-Yeung, C. L. (2020). Targeting dopamine receptor d2 by imipridone suppresses uterine serous cancer malignant phenotype. Cancers, 12(9), 1-17. Article 2436. https://doi.org/10.3390/cancers12092436

@article{90bd9dde5e6546dda5d2bea2b0a0757f,

title = "Targeting dopamine receptor d2 by imipridone suppresses uterine serous cancer malignant phenotype",

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.",

keywords = "Dopamine receptor D2, Imipridone, Metabolic reprogramming, Uterine serous cancer",

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

note = "Publisher Copyright: {\textcopyright} 2020 by the authors. Licensee MDPI, Basel, Switzerland.",

year = "2020",

month = sep,

doi = "10.3390/cancers12092436",

language = "English (US)",

volume = "12",

pages = "1--17",

journal = "Cancers",

issn = "2072-6694",

publisher = "Multidisciplinary Digital Publishing Institute (MDPI)",

number = "9",

}

TY - JOUR

T1 - Targeting dopamine receptor d2 by imipridone suppresses uterine serous cancer malignant phenotype

AU - Hu, Wen

AU - Zhang, Li

AU - Ferri-Borgogno, Sammy

AU - Kwan, Suet Ying

AU - Lewis, Kelsey E.

AU - Cun, Han T.

AU - Yeung, Tsz Lun

AU - Soliman, Pamela T.

AU - Tarapore, Rohinton S.

AU - Allen, Joshua E.

AU - Guan, Xinyuan

AU - Lu, Karen H.

AU - Mok, Samuel C.

AU - Au-Yeung, Chi Lam

PY - 2020/9

Y1 - 2020/9

N2 - 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.

AB - 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.

KW - Dopamine receptor D2

KW - Imipridone

KW - Metabolic reprogramming

KW - Uterine serous cancer

UR - http://www.scopus.com/inward/record.url?scp=85092331153&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85092331153&partnerID=8YFLogxK

U2 - 10.3390/cancers12092436

DO - 10.3390/cancers12092436

M3 - Article

C2 - 32867127

AN - SCOPUS:85092331153

SN - 2072-6694

VL - 12

SP - 1

EP - 17

JO - Cancers

JF - Cancers

IS - 9

M1 - 2436

ER -

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

Abstract

Keywords

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this