{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,18]],"date-time":"2026-07-18T03:10:07Z","timestamp":1784344207200,"version":"3.55.0"},"reference-count":330,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2024,7,16]],"date-time":"2024-07-16T00:00:00Z","timestamp":1721088000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"la Region Occitanie Pyr\u00e9n\u00e9es-M\u00e9diterran\u00e9e","award":["R22064FB\/RPH22006FBA"],"award-info":[{"award-number":["R22064FB\/RPH22006FBA"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Despite significant progress in cancer prevention, screening, and treatment, the still limited number of therapeutic options is an obstacle towards increasing the cancer cure rate. In recent years, many efforts were put forth to develop therapeutics that selectively target different components of the oncogenic Wnt\/\u03b2-catenin signaling pathway. These include small molecule inhibitors, antibodies, and more recently, gene-based approaches. Although some of them showed promising outcomes in clinical trials, the Wnt\/\u03b2-catenin pathway is still not targeted in routine clinical practice for cancer management. As for most anticancer treatments, a critical limitation to the use of Wnt\/\u03b2-catenin inhibitors is their therapeutic index, i.e., the difficulty of combining effective anticancer activity with acceptable toxicity. Protecting healthy tissues from the effects of Wnt\/\u03b2-catenin inhibitors is a major issue due to the vital role of the Wnt\/\u03b2-catenin signaling pathway in adult tissue homeostasis and regeneration. In this review, we provide an up-to-date summary of clinical trials on Wnt\/\u03b2-catenin pathway inhibitors, examine their anti-tumor activity and associated adverse events, and explore strategies under development to improve the benefit\/risk profile of this therapeutic approach.<\/jats:p>","DOI":"10.3390\/ph17070949","type":"journal-article","created":{"date-parts":[[2024,7,16]],"date-time":"2024-07-16T15:05:51Z","timestamp":1721142351000},"page":"949","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Why Is Wnt\/\u03b2-Catenin Not Yet Targeted in Routine Cancer Care?"],"prefix":"10.3390","volume":"17","author":[{"given":"Auriane","family":"de Pellegars-Malhortie","sequence":"first","affiliation":[{"name":"IRCM (Montpellier Cancer Research Institute), University of Montpellier, Inserm, ICM (Montpellier Regional Cancer Institute), 34298 Montpellier, CEDEX 5, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laurence","family":"Picque Lasorsa","sequence":"additional","affiliation":[{"name":"IRCM (Montpellier Cancer Research Institute), University of Montpellier, Inserm, ICM (Montpellier Regional Cancer Institute), 34298 Montpellier, CEDEX 5, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5644-9603","authenticated-orcid":false,"given":"Thibault","family":"Mazard","sequence":"additional","affiliation":[{"name":"IRCM (Montpellier Cancer Research Institute), University of Montpellier, Inserm, ICM (Montpellier Regional Cancer Institute), 34298 Montpellier, CEDEX 5, France"},{"name":"Medical Oncology Department, ICM, University of Montpellier, CEDEX 5, 34298 Montpellier, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabien","family":"Granier","sequence":"additional","affiliation":[{"name":"FGHI, 165 Rue Denis Papin, 34570 Montarnaud, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7553-087X","authenticated-orcid":false,"given":"Corinne","family":"Pr\u00e9vostel","sequence":"additional","affiliation":[{"name":"IRCM (Montpellier Cancer Research Institute), University of Montpellier, Inserm, ICM (Montpellier Regional Cancer Institute), 34298 Montpellier, CEDEX 5, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,7,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1016\/0092-8674(84)90209-5","article-title":"Structure and Nucleotide Sequence of the Putative Mammary Oncogene Int-1; Proviral Insertions Leave the Protein-Encoding Domain Intact","volume":"39","author":"Nusse","year":"1984","journal-title":"Cell"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1126\/science.84.2172.162.a","article-title":"Some Possible Effects of Nursing on the Mammary Gland Tumor Incidence in Mice","volume":"84","author":"Bittner","year":"1936","journal-title":"Science"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1141","DOI":"10.1038\/1941141a0","article-title":"Purification of the Mouse Mammary Tumour Virus","volume":"194","author":"Lyons","year":"1962","journal-title":"Nature"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1016\/0092-8674(82)90409-3","article-title":"Many Tumors Induced by the Mouse Mammary Tumor Virus Contain a Provirus Integrated in the Same Region of the Host Genome","volume":"31","author":"Nusse","year":"1982","journal-title":"Cell"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1101\/gad.317412.118","article-title":"A ZNRF3-Dependent Wnt\/\u03b2-Catenin Signaling Gradient Is Required for Adrenal Homeostasis","volume":"33","author":"Basham","year":"2019","journal-title":"Genes Dev."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"2905","DOI":"10.1002\/j.1460-2075.1985.tb04021.x","article-title":"The Nucleotide Sequence of the Human Int-1 Mammary Oncogene; Evolutionary Conservation of Coding and Non-Coding Sequences","volume":"4","author":"Kwee","year":"1985","journal-title":"EMBO J."},{"key":"ref_7","first-page":"3337","article-title":"Nucleotide Sequence and Expression In Vitro of cDNA Derived from mRNA of int-1, a Provirally Activated Mouse Mammary Oncogene","volume":"5","author":"Fung","year":"1985","journal-title":"Mol. 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