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Growing evidence suggests a critical role of PLK4 in the development and progression of various cancers. In many cancer types, its upregulation leads to pro-oncogenic phenotypes, while its pharmacologic inhibition leads to anticancer effects. Functionally, PLK4 affects cancer cell proliferation, growth, motility, invasion, migration, epithelial-mesenchymal transition, apoptosis and other critical oncogenic processes. In breast cancer, PLK4 is associated with centrosome amplification, aneuploidy and chromosomal instability, promoting invasive phenotypes and resistance to cancer cell death. PLK4 shows great promise as a prognostic and predictive biomarker in breast cancer. It is commonly found to be overexpressed in primary human breast cancers and is associated with poor oncologic outcomes, clinicopathologic parameters, and high-risk subtypes. Various compounds, such as CFI-400945, centrinone B, and others have been developed to inhibit PLK4 activity. Preclinical studies have shown that PLK4 inhibitors lead to decreased proliferation, growth and migration and increased breast cancer cell death. Moreover, PLK4 inhibition can serve to enhance the effects of other treatments, including radiotherapy. Clinical studies have been initiated with some of these compounds in cancer patients, including those with breast cancer. This manuscript discusses the role of PLK4 as a promising therapeutic target in breast cancer, one of the most common causes of morbidity and mortality in women.<\/jats:p>","DOI":"10.1093\/carcin\/bgaf067","type":"journal-article","created":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T11:57:09Z","timestamp":1760183829000},"source":"Crossref","is-referenced-by-count":1,"title":["Polo-like kinase 4 (PLK4) as a therapeutic target in breast cancer"],"prefix":"10.1093","volume":"46","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0084-8733","authenticated-orcid":false,"given":"Armen","family":"Parsyan","sequence":"first","affiliation":[{"name":"Department of Anatomy and Cell Biology, Schulich School of Medicine & Dentistry, Western University , London, ON N6A 5C1 ,","place":["Canada"]},{"name":"Verspeeten Family Cancer Centre, London Health Sciences Centre and London Health Sciences Centre Research Institute , London, ON N6A 5W9 ,","place":["Canada"]},{"name":"Department of Oncology, Schulich School of Medicine & Dentistry, Western University , London, ON N6A 5W9 ,","place":["Canada"]},{"name":"Department of Surgery, Schulich School of Medicine & Dentistry , London, ON N6A 4V2 ,","place":["Canada"]},{"name":"St Joseph\u2019s Health Care , London, ON N6A 4V2 ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-9808-2837","authenticated-orcid":false,"given":"Harjot","family":"Athwal","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Cell Biology, Schulich School of Medicine & Dentistry, Western University , London, ON N6A 5C1 ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2228-6217","authenticated-orcid":false,"given":"Vasudeva","family":"Bhat","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Cell Biology, Schulich School of Medicine & Dentistry, Western University , London, ON N6A 5C1 ,","place":["Canada"]},{"name":"Verspeeten Family Cancer Centre, London Health Sciences Centre and London Health Sciences Centre Research Institute , London, ON N6A 5W9 ,","place":["Canada"]},{"name":"Department of Oncology, Schulich School of Medicine & Dentistry, Western University , London, ON N6A 5W9 ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0344-1181","authenticated-orcid":false,"given":"Alison L","family":"Allan","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Cell Biology, Schulich School of Medicine & Dentistry, Western University , London, ON N6A 5C1 ,","place":["Canada"]},{"name":"Verspeeten Family Cancer Centre, London Health Sciences Centre and London Health Sciences Centre Research Institute , London, ON N6A 5W9 ,","place":["Canada"]},{"name":"Department of Oncology, Schulich School of Medicine & Dentistry, Western University , London, ON N6A 5W9 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