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

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...

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Published in:	Frontiers in oncology Vol. 12; p. 852260
Main Authors:	Wang, Wenyu, Cho, Untack, Yoo, Anna, Jung, Chae-Lim, Kim, Boyun, Kim, Heeyeon, Lee, Juwon, Jo, HyunA, Han, Youngjin, Song, Myoung-Hyun, Lee, Ja-Oh, Kim, Se Ik, Lee, Maria, Ku, Ja-Lok, Lee, Cheol, Song, Yong Sang
Format:	Journal Article
Language:	English
Published:	Switzerland Frontiers Media S.A 12-05-2022
Subjects:	CWP232291 Oncology organoids ovarian cancer targeted therapy Wnt/β-catenin targeted therapy ovarian cancer Wnt/β-catenin organoids CWP232291
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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 , and 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.
AbstractList	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 , and 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. 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. 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.
Author	Jung, Chae-Lim Cho, Untack Ku, Ja-Lok Lee, Maria Kim, Se Ik Lee, Cheol Lee, Juwon Wang, Wenyu Song, Myoung-Hyun Yoo, Anna Song, Yong Sang Kim, Heeyeon Jo, HyunA Kim, Boyun Han, Youngjin Lee, Ja-Oh
AuthorAffiliation	1 Interdisciplinary Program in Cancer Biology, Seoul National University College of Medicine , Seoul , South Korea 3 Drug Discovery Center, JW Pharmaceutical Corporation , Seoul , South Korea 8 Department of Obstetrics and Gynecology, Seoul National University College of Medicine , Seoul , South Korea 4 Department of Biosafety, College of Life and Health Science, Kyungsung University , Busan , South Korea 7 Korean Cell Line Bank, Laboratory of Cell Biology, Cancer Research Institute, Seoul National University College of Medicine , Seoul , South Korea 2 Cancer Research Institute, Seoul National University College of Medicine , Seoul , South Korea 6 Department of Biomedical Sciences, Seoul National University College of Medicine , Seoul , South Korea 9 Department of Pathology, Seoul National University College of Medicine , Seoul , South Korea 5 WCU Biomodulation, Department of Agricultural Biotechnology, Seoul National University , Seoul , South Korea
AuthorAffiliation_xml	– name: 2 Cancer Research Institute, Seoul National University College of Medicine , Seoul , South Korea – name: 5 WCU Biomodulation, Department of Agricultural Biotechnology, Seoul National University , Seoul , South Korea – name: 4 Department of Biosafety, College of Life and Health Science, Kyungsung University , Busan , South Korea – name: 1 Interdisciplinary Program in Cancer Biology, Seoul National University College of Medicine , Seoul , South Korea – name: 6 Department of Biomedical Sciences, Seoul National University College of Medicine , Seoul , South Korea – name: 9 Department of Pathology, Seoul National University College of Medicine , Seoul , South Korea – name: 7 Korean Cell Line Bank, Laboratory of Cell Biology, Cancer Research Institute, Seoul National University College of Medicine , Seoul , South Korea – name: 3 Drug Discovery Center, JW Pharmaceutical Corporation , Seoul , South Korea – name: 8 Department of Obstetrics and Gynecology, Seoul National University College of Medicine , Seoul , South Korea
Author_xml	– sequence: 1 givenname: Wenyu surname: Wang fullname: Wang, Wenyu organization: Cancer Research Institute, Seoul National University College of Medicine, Seoul, South Korea – sequence: 2 givenname: Untack surname: Cho fullname: Cho, Untack organization: Cancer Research Institute, Seoul National University College of Medicine, Seoul, South Korea – sequence: 3 givenname: Anna surname: Yoo fullname: Yoo, Anna organization: Drug Discovery Center, JW Pharmaceutical Corporation, Seoul, South Korea – sequence: 4 givenname: Chae-Lim surname: Jung fullname: Jung, Chae-Lim organization: Drug Discovery Center, JW Pharmaceutical Corporation, Seoul, South Korea – sequence: 5 givenname: Boyun surname: Kim fullname: Kim, Boyun organization: Department of Biosafety, College of Life and Health Science, Kyungsung University, Busan, South Korea – sequence: 6 givenname: Heeyeon surname: Kim fullname: Kim, Heeyeon organization: WCU Biomodulation, Department of Agricultural Biotechnology, Seoul National University, Seoul, South Korea – sequence: 7 givenname: Juwon surname: Lee fullname: Lee, Juwon organization: WCU Biomodulation, Department of Agricultural Biotechnology, Seoul National University, Seoul, South Korea – sequence: 8 givenname: HyunA surname: Jo fullname: Jo, HyunA organization: WCU Biomodulation, Department of Agricultural Biotechnology, Seoul National University, Seoul, South Korea – sequence: 9 givenname: Youngjin surname: Han fullname: Han, Youngjin organization: Cancer Research Institute, Seoul National University College of Medicine, Seoul, South Korea – sequence: 10 givenname: Myoung-Hyun surname: Song fullname: Song, Myoung-Hyun organization: Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, South Korea – sequence: 11 givenname: Ja-Oh surname: Lee fullname: Lee, Ja-Oh organization: Korean Cell Line Bank, Laboratory of Cell Biology, Cancer Research Institute, Seoul National University College of Medicine, Seoul, South Korea – sequence: 12 givenname: Se Ik surname: Kim fullname: Kim, Se Ik organization: Department of Obstetrics and Gynecology, Seoul National University College of Medicine, Seoul, South Korea – sequence: 13 givenname: Maria surname: Lee fullname: Lee, Maria organization: Department of Obstetrics and Gynecology, Seoul National University College of Medicine, Seoul, South Korea – sequence: 14 givenname: Ja-Lok surname: Ku fullname: Ku, Ja-Lok organization: Korean Cell Line Bank, Laboratory of Cell Biology, Cancer Research Institute, Seoul National University College of Medicine, Seoul, South Korea – sequence: 15 givenname: Cheol surname: Lee fullname: Lee, Cheol organization: Department of Pathology, Seoul National University College of Medicine, Seoul, South Korea – sequence: 16 givenname: Yong Sang surname: Song fullname: Song, Yong Sang organization: Department of Obstetrics and Gynecology, Seoul National University College of Medicine, Seoul, South Korea
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Cites_doi	10.1016/j.humpath.2009.04.017 10.1038/onc.2017.185 10.1038/modpathol.2009.141 10.1016/0925-4773(96)00597-7 10.1126/science.aaw6985 10.1186/1757-2215-7-16 10.1016/j.cell.2012.05.012 10.1038/nrd4233 10.1007/s11912-019-0763-9 10.1007/s12032-017-1026-y 10.18632/oncotarget.3934 10.1002/ijc.28768 10.1038/onc.2014.178 10.3322/caac.21660 10.1101/gad.1957710 10.18632/oncotarget.23695 10.1182/bloodadvances.2019000757 10.1093/annonc/mdy157 10.3802/jgo.2013.24.1.83 10.1038/s12276-020-0380-6 10.1016/j.clml.2015.08.084 10.3390/diagnostics11030452 10.3390/antiox9111137 10.1200/JCO.2017.35.15_suppl.e15534 10.1186/s13045-019-0832-4 10.1093/annonc/mdw094 10.1097/OGX.0000000000000962 10.1016/j.ygyno.2013.09.034 10.1200/jco.2016.34.4_suppl.594 10.1016/j.prp.2017.05.011 10.1002/mc.23064 10.1093/jnci/djq279 10.1016/S0092-8674(00)80112-9 10.1038/s41388-019-0949-5 10.1056/NEJMoa1810858 10.1007/s00280-017-3501-8 10.1186/s13045-017-0471-6 10.3892/ijo.2017.4129 10.1101/cshperspect.a007898 10.1016/j.biopha.2018.11.082 10.1186/s13046-019-1451-1
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Copyright	Copyright © 2022 Wang, Cho, Yoo, Jung, Kim, Kim, Lee, Jo, Han, Song, Lee, Kim, Lee, Ku, Lee and Song. Copyright © 2022 Wang, Cho, Yoo, Jung, Kim, Kim, Lee, Jo, Han, Song, Lee, Kim, Lee, Ku, Lee and Song 2022 Wang, Cho, Yoo, Jung, Kim, Kim, Lee, Jo, Han, Song, Lee, Kim, Lee, Ku, Lee and Song
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Keywords	targeted therapy ovarian cancer Wnt/β-catenin organoids CWP232291
Language	English
License	Copyright © 2022 Wang, Cho, Yoo, Jung, Kim, Kim, Lee, Jo, Han, Song, Lee, Kim, Lee, Ku, Lee and Song. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
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Notes	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Edited by: Marie R. Webster, Lankenau Institute for Medical Research, United States Reviewed by: Arunasalam Dharmarajan, Sri Ramachandra Institute of Higher Education and Research, India; Dong-Joo (Ellen) Cheon, Albany Medical College, United States This article was submitted to Cancer Molecular Targets and Therapeutics, a section of the journal Frontiers in Oncology
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Snippet	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...
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SubjectTerms	CWP232291 Oncology organoids ovarian cancer targeted therapy Wnt/β-catenin
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Title	Wnt/β-Catenin Inhibition by CWP232291 as a Novel Therapeutic Strategy in Ovarian Cancer
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