Wnt/β-Catenin Inhibition by CWP232291 as a Novel Therapeutic Strategy in Ovarian Cancer

Wenyu Wang; Untack Cho; Anna Yoo; Chae-Lim Jung; Boyun Kim; Heeyeon Kim; Juwon Lee; HyunA Jo; Youngjin Han; Myoung-Hyun Song; Ja-Oh Lee; Se Ik Kim; Maria Lee; Ja-Lok Ku; Cheol Lee; Yong Sang Song

doi:10.3389/fonc.2022.852260

Wnt/β-Catenin Inhibition by CWP232291 as a Novel Therapeutic Strategy in Ovarian Cancer

Front Oncol. 2022 May 12:12:852260. doi: 10.3389/fonc.2022.852260. eCollection 2022.

Authors

Wenyu Wang^{1

2}, Untack Cho^{1

2}, Anna Yoo³, Chae-Lim Jung³, Boyun Kim⁴, Heeyeon Kim^{2

5}, Juwon Lee^{2

5}, HyunA Jo^{2

5}, Youngjin Han², Myoung-Hyun Song⁶, Ja-Oh Lee⁷, Se Ik Kim⁸, Maria Lee⁸, Ja-Lok Ku^{6

7}, Cheol Lee⁹, Yong Sang Song^{1

2

5

8}

Affiliations

¹ Interdisciplinary Program in Cancer Biology, Seoul National University College of Medicine, Seoul, South Korea.
² Cancer Research Institute, Seoul National University College of Medicine, Seoul, South Korea.
³ Drug Discovery Center, JW Pharmaceutical Corporation, Seoul, South Korea.
⁴ Department of Biosafety, College of Life and Health Science, Kyungsung University, Busan, South Korea.
⁵ WCU Biomodulation, Department of Agricultural Biotechnology, Seoul National University, Seoul, South Korea.
⁶ Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, South Korea.
⁷ Korean Cell Line Bank, Laboratory of Cell Biology, Cancer Research Institute, Seoul National University College of Medicine, Seoul, South Korea.
⁸ Department of Obstetrics and Gynecology, Seoul National University College of Medicine, Seoul, South Korea.
⁹ Department of Pathology, Seoul National University College of Medicine, Seoul, South Korea.

Abstract

The poor prognosis of ovarian cancer patients mainly results from a lack of early diagnosis approaches and a high rate of relapse. Only a very modest improvement has been made in ovarian cancer patient survival with traditional treatments. More targeted therapies precisely matching each patient are strongly needed. The aberrant activation of Wnt/β-catenin signaling pathway plays a fundamental role in cancer development and progression in various types of cancer including ovarian cancer. Recent insight into this pathway has revealed the potential of targeting Wnt/β-catenin in ovarian cancer treatment. This study aims to investigate the effect of CWP232291, a small molecular Wnt/β-catenin inhibitor on ovarian cancer progression. Various in vitro, in vivo and ex vivo models are established for CWP232291 testing. Results show that CWP232291 could significantly attenuate ovarian cancer growth through inhibition of β-catenin. Noticeably, CWP232291 could also s suppress the growth of cisplatin-resistant cell lines and ovarian cancer patient-derived organoids. Overall, this study has firstly demonstrated the anti-tumor effect of CWP232291 in ovarian cancer and proposed Wnt/β-catenin pathway inhibition as a novel therapeutic strategy against ovarian cancer.

Keywords: CWP232291; Wnt/β-catenin; organoids; ovarian cancer; targeted therapy.