Beyond TNBC: Repositioning of Clofazimine Against a Broad Range of Wnt-Dependent Cancers
Wnt signaling plays key roles in oncogenic transformation and progression in a number of cancer types, including tumors in the breast, colon, ovaries, liver, and other tissues. Despite this importance, no therapy targeting the Wnt pathway currently exists. We have previously shown that the anti-myco...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2020-12-01
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| Series: | Frontiers in Oncology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2020.602817/full |
| _version_ | 1818594811100266496 |
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| author | Jiabin Xu Jiabin Xu Alexey Koval Vladimir L. Katanaev Vladimir L. Katanaev Vladimir L. Katanaev |
| author_facet | Jiabin Xu Jiabin Xu Alexey Koval Vladimir L. Katanaev Vladimir L. Katanaev Vladimir L. Katanaev |
| author_sort | Jiabin Xu |
| collection | DOAJ |
| description | Wnt signaling plays key roles in oncogenic transformation and progression in a number of cancer types, including tumors in the breast, colon, ovaries, liver, and other tissues. Despite this importance, no therapy targeting the Wnt pathway currently exists. We have previously shown that the anti-mycobacterium drug clofazimine is a specific inhibitor of Wnt signaling and cell proliferation in triple-negative breast cancer (TNBC). Here, we expand the applicability of clofazimine to a set of other Wnt-dependent cancers. Using a panel of cell lines from hepatocellular carcinoma, glioblastoma, as well as colorectal and ovarian cancer, we show that the efficacy of clofazimine against a given cancer type correlates with the basal levels of Wnt pathway activation and the ability of the drug to inhibit Wnt signaling in it, being further influenced by the cancer mutational spectrum. Our study establishes the basis for patient stratification in the future clinical trials of clofazimine and may ultimately contribute to the establishment of the Wnt pathway-targeted therapy against a diverse set of cancer types relying on the oncogenic Wnt signaling. |
| first_indexed | 2024-12-16T11:06:03Z |
| format | Article |
| id | doaj.art-3493d40b3d164a83aaa6dbeba9b12d6a |
| institution | Directory Open Access Journal |
| issn | 2234-943X |
| language | English |
| last_indexed | 2024-12-16T11:06:03Z |
| publishDate | 2020-12-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj.art-3493d40b3d164a83aaa6dbeba9b12d6a2022-12-21T22:33:51ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2020-12-011010.3389/fonc.2020.602817602817Beyond TNBC: Repositioning of Clofazimine Against a Broad Range of Wnt-Dependent CancersJiabin Xu0Jiabin Xu1Alexey Koval2Vladimir L. Katanaev3Vladimir L. Katanaev4Vladimir L. Katanaev5Translational Research Center in Oncohaematology, Department of Cell Physiology and Metabolism, Faculty of Medicine, University of Geneva, Geneva, SwitzerlandDepartment of Biomedical Sciences, Faculty of Biology and Medicine, University of Lausanne, Lausanne, SwitzerlandTranslational Research Center in Oncohaematology, Department of Cell Physiology and Metabolism, Faculty of Medicine, University of Geneva, Geneva, SwitzerlandTranslational Research Center in Oncohaematology, Department of Cell Physiology and Metabolism, Faculty of Medicine, University of Geneva, Geneva, SwitzerlandSchool of Biomedicine, Far Eastern Federal University, Vladivostok, RussiaInstitute of Oceanography, Minjiang University, Fuzhou, ChinaWnt signaling plays key roles in oncogenic transformation and progression in a number of cancer types, including tumors in the breast, colon, ovaries, liver, and other tissues. Despite this importance, no therapy targeting the Wnt pathway currently exists. We have previously shown that the anti-mycobacterium drug clofazimine is a specific inhibitor of Wnt signaling and cell proliferation in triple-negative breast cancer (TNBC). Here, we expand the applicability of clofazimine to a set of other Wnt-dependent cancers. Using a panel of cell lines from hepatocellular carcinoma, glioblastoma, as well as colorectal and ovarian cancer, we show that the efficacy of clofazimine against a given cancer type correlates with the basal levels of Wnt pathway activation and the ability of the drug to inhibit Wnt signaling in it, being further influenced by the cancer mutational spectrum. Our study establishes the basis for patient stratification in the future clinical trials of clofazimine and may ultimately contribute to the establishment of the Wnt pathway-targeted therapy against a diverse set of cancer types relying on the oncogenic Wnt signaling.https://www.frontiersin.org/articles/10.3389/fonc.2020.602817/fullWntrepositioningclofaziminecolorectal cancerovarian cancerhepatocellular carcinoma |
| spellingShingle | Jiabin Xu Jiabin Xu Alexey Koval Vladimir L. Katanaev Vladimir L. Katanaev Vladimir L. Katanaev Beyond TNBC: Repositioning of Clofazimine Against a Broad Range of Wnt-Dependent Cancers Frontiers in Oncology Wnt repositioning clofazimine colorectal cancer ovarian cancer hepatocellular carcinoma |
| title | Beyond TNBC: Repositioning of Clofazimine Against a Broad Range of Wnt-Dependent Cancers |
| title_full | Beyond TNBC: Repositioning of Clofazimine Against a Broad Range of Wnt-Dependent Cancers |
| title_fullStr | Beyond TNBC: Repositioning of Clofazimine Against a Broad Range of Wnt-Dependent Cancers |
| title_full_unstemmed | Beyond TNBC: Repositioning of Clofazimine Against a Broad Range of Wnt-Dependent Cancers |
| title_short | Beyond TNBC: Repositioning of Clofazimine Against a Broad Range of Wnt-Dependent Cancers |
| title_sort | beyond tnbc repositioning of clofazimine against a broad range of wnt dependent cancers |
| topic | Wnt repositioning clofazimine colorectal cancer ovarian cancer hepatocellular carcinoma |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2020.602817/full |
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