{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T09:48:22Z","timestamp":1786960102473,"version":"build-2736575974"},"reference-count":102,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2025,7,18]],"date-time":"2025-07-18T00:00:00Z","timestamp":1752796800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"FAPERJ (Rio de Janeiro State Research Support Foundation)","award":["SEI-260002\/007142\/2024"],"award-info":[{"award-number":["SEI-260002\/007142\/2024"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>Background\/Objective: Cancer stem cells (CSCs) are a self-renewing subpopulation within tumors that contribute to heterogeneity and resistance to conventional cancer therapies, including chemotherapy and radiotherapy. Despite growing interest in CSCs as therapeutic targets, effective compounds against these cells remain limited. This systematic review aims to assess the potential of metal-based coordination complexes as anti-CSC agents in preclinical models. Methods: A systematic literature search was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Twenty-seven original in vitro studies were included, all evaluating the cytotoxic effects of metal-based compounds on cancer cell lines enriched with CSC subpopulations. To ensure methodological rigor, all articles underwent a critical appraisal by independent reviewers who resolved discrepancies through consensus, and only studies meeting predefined quality criteria were included. Results: Several metal complexes, particularly copper-based compounds, demonstrated significant cytotoxicity toward CSCs, mainly through the induction of apoptosis. Breast cancer was the most frequently studied tumor type. Many studies reported modulation of CSC-related markers, including EPCAM, CD44, CD133, CD24, SOX2, KLF4, Oct4, NOTCH1, ALDH1, CXCR4, and HES1, suggesting effects on CSC maintenance pathways. Most studies were conducted in the United Kingdom and relied on in vitro models. Conclusions: Metal coordination complexes, especially those containing copper, show promise as therapeutic agents targeting CSCs. However, further in vivo studies and mechanistic investigations are essential to advance their translational potential.<\/jats:p>","DOI":"10.3390\/pharmaceutics17070931","type":"journal-article","created":{"date-parts":[[2025,7,18]],"date-time":"2025-07-18T13:33:27Z","timestamp":1752845607000},"page":"931","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Preclinical Trials of Cancer Stem Cells Targeted by Metal-Based Coordination Complexes: A Systematic Review"],"prefix":"10.3390","volume":"17","author":[{"given":"Ana Caroline Mafra","family":"Bezerra","sequence":"first","affiliation":[{"name":"Center for Biosciences and Biotechnology, Darcy Ribeiro State University of Northern Fluminense, Campos dos Goytacazes 28013-602, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucas Elohim Cardoso Viana","family":"Baptista","sequence":"additional","affiliation":[{"name":"Center for Biosciences and Biotechnology, Darcy Ribeiro State University of Northern Fluminense, Campos dos Goytacazes 28013-602, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria N\u00fabia Alencar","family":"Couto","sequence":"additional","affiliation":[{"name":"Center for Biosciences and Biotechnology, Darcy Ribeiro State University of Northern Fluminense, Campos dos Goytacazes 28013-602, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5134-7341","authenticated-orcid":false,"given":"Milton Masahiko","family":"Kanashiro","sequence":"additional","affiliation":[{"name":"Center for Biosciences and Biotechnology, Darcy Ribeiro State University of Northern Fluminense, Campos dos Goytacazes 28013-602, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,7,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"229","DOI":"10.3322\/caac.21834","article-title":"Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"74","author":"Bray","year":"2024","journal-title":"CA Cancer J Clin."},{"key":"ref_2","unstructured":"World Health Organization (2022). 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