{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,9]],"date-time":"2026-05-09T05:10:27Z","timestamp":1778303427678,"version":"3.51.4"},"reference-count":92,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,4,25]],"date-time":"2026-04-25T00:00:00Z","timestamp":1777075200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Dickkopf-1 (DKK1) is a secreted glycoprotein that traditionally acts as an antagonist of canonical Wnt\/\u03b2-catenin signaling. Although it functions as a tumor suppressor in some specific biological background and disease stages, growing evidence links DKK1 to tumor progression, immune evasion, and therapy resistance in a variety of multiple malignancies. This review provides a comprehensive bench-to-bedside overview of DKK1 in cancer. We first delineate how DKK1 regulates both Wnt-dependent and Wnt-independent pathways. From a clinical perspective, we evaluate the application potential of DKK1 as a diagnostic and prognostic biomarker. We further discuss the progress of DKK1-targeted interventions, ranging from monoclonal antibodies in clinical trials to next-generation therapeutic modalities. Finally, we discuss the challenges in clinical translation and suggest future directions for DKK1-based precision medicine. In summary, by integrating preclinical insights with current clinical data, this review provides a strategic roadmap for advancing DKK1-targeted therapies in cancer.<\/jats:p>","DOI":"10.3390\/cancers18091375","type":"journal-article","created":{"date-parts":[[2026,4,27]],"date-time":"2026-04-27T19:24:51Z","timestamp":1777317891000},"page":"1375","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["DKK1 in Cancer: A Bench-to-Bedside Review of Molecular Mechanisms and Clinical Applications"],"prefix":"10.3390","volume":"18","author":[{"given":"Meiheng","family":"Sun","sequence":"first","affiliation":[{"name":"School of Chinese Medicine, The Chinese University of Hong Kong, Hong Kong, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuzhe","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Oncology, Shanghai Municipal Hospital of Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 200071, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yihao","family":"Zhang","sequence":"additional","affiliation":[{"name":"School of Chinese Medicine, The Chinese University of Hong Kong, Hong Kong, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ziqi","family":"Chen","sequence":"additional","affiliation":[{"name":"Law Sau Fai Institute for Advancing Translational Medicine in Bone & Joint Diseases, Hong Kong Baptist University, Hong Kong, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuanyuan","family":"Yu","sequence":"additional","affiliation":[{"name":"Law Sau Fai Institute for Advancing Translational Medicine in Bone & Joint Diseases, Hong Kong Baptist University, Hong Kong, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aiping","family":"Lu","sequence":"additional","affiliation":[{"name":"Law Sau Fai Institute for Advancing Translational Medicine in Bone & Joint Diseases, Hong Kong Baptist University, Hong Kong, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4651-677X","authenticated-orcid":false,"given":"Wei","family":"Kang","sequence":"additional","affiliation":[{"name":"Department of Anatomical and Cellular Pathology, State Key Laboratory of Translational Oncology, Sir Y.K. Pao Cancer Center, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qianjun","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Breast, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou 510120, China"},{"name":"State Key Laboratory of Traditional Chinese Medicine Syndrome, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou 510120, China"},{"name":"Chinese Medicine Guangdong Laboratory, Guangzhou 510006, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7807-7695","authenticated-orcid":false,"given":"Ge","family":"Zhang","sequence":"additional","affiliation":[{"name":"Law Sau Fai Institute for Advancing Translational Medicine in Bone & Joint Diseases, Hong Kong Baptist University, Hong Kong, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jianhui","family":"Tian","sequence":"additional","affiliation":[{"name":"Department of Oncology, Shanghai Municipal Hospital of Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 200071, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bao-Ting","family":"Zhang","sequence":"additional","affiliation":[{"name":"School of Chinese Medicine, The Chinese University of Hong Kong, Hong Kong, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1038\/34848","article-title":"Dickkopf-1 is a member of a new family of secreted proteins and functions in head induction","volume":"391","author":"Glinka","year":"1998","journal-title":"Nature"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1038\/nm1538","article-title":"Dickkopf-1 is a master regulator of joint remodeling","volume":"13","author":"Diarra","year":"2007","journal-title":"Nat. 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