{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,30]],"date-time":"2026-08-30T22:28:35Z","timestamp":1788128915206,"version":"build-2803163510"},"reference-count":154,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2025,4,24]],"date-time":"2025-04-24T00:00:00Z","timestamp":1745452800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"South African Medical Research Council","award":["23108"],"award-info":[{"award-number":["23108"]}]},{"name":"South African Medical Research Council","award":["138139"],"award-info":[{"award-number":["138139"]}]},{"name":"National Research Foundation","award":["23108"],"award-info":[{"award-number":["23108"]}]},{"name":"National Research Foundation","award":["138139"],"award-info":[{"award-number":["138139"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Thyroid cancer (TC) is a significant global health issue that exhibits notable heterogeneity in incidence and outcomes. In low-resource settings such as Africa, delayed diagnosis and limited healthcare access exacerbate mortality rates. Among follicular cell-derived thyroid cancers\u2014including papillary (PTC), follicular (FTC), anaplastic (ATC), and poorly differentiated (PDTC) subtypes\u2014the role of CD44 variants has emerged as a critical factor influencing tumor progression and multidrug resistance (MDR). CD44, a transmembrane glycoprotein, and its splice variants (CD44v) mediate cell adhesion, migration, and survival, contributing to cancer stem cell (CSC) maintenance and therapy resistance. Differential expression patterns of CD44 isoforms across TC subtypes have shown diagnostic, prognostic, and therapeutic implications. Specifically, CD44v6 expression in PTC has been correlated with metastasis and aggressive tumor behavior, while in FTC, its expression aids in distinguishing malignant from benign lesions. Furthermore, CD44 contributes to MDR through enhanced drug efflux via ABC transporters, apoptosis evasion, and CSC maintenance via the Wnt\/\u03b2-catenin and PI3K\/Akt pathways. Targeted therapies against CD44 such as monoclonal antibodies, hyaluronic acid-based nanocarriers, and gene-editing technologies hold promise in overcoming MDR. However, despite the mounting evidence supporting CD44-targeted strategies in various cancers, research on this therapeutic potential in TC remains limited. This review synthesizes existing knowledge on CD44 variant expression in follicular cell-derived thyroid cancers and highlights potential therapeutic strategies to mitigate MDR, particularly in high-burden regions, thereby improving patient outcomes and survival.<\/jats:p>","DOI":"10.3390\/molecules30091899","type":"journal-article","created":{"date-parts":[[2025,4,24]],"date-time":"2025-04-24T09:26:58Z","timestamp":1745486818000},"page":"1899","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["CD44 Variant Expression in Follicular Cell-Derived Thyroid Cancers: Implications for Overcoming Multidrug Resistance"],"prefix":"10.3390","volume":"30","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5588-3221","authenticated-orcid":false,"given":"Benny","family":"Mosoane","sequence":"first","affiliation":[{"name":"Department of Anatomical Pathology, Faculty of Health Sciences, University of Pretoria, Pretoria 0001, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michelle","family":"McCabe","sequence":"additional","affiliation":[{"name":"Department of Anatomical Pathology, Faculty of Health Sciences, University of Pretoria, Pretoria 0001, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brandon S.","family":"Jackson","sequence":"additional","affiliation":[{"name":"Breast and Endocrine Unit, Department of General Surgery, University of Pretoria, Kalafong Provincial Tertiary Hospital, Pretoria 0001, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8012-3646","authenticated-orcid":false,"given":"Zodwa","family":"Dlamini","sequence":"additional","affiliation":[{"name":"SAMRC Precision Oncology Research Unit (PORU), DSI\/NRF SARChI Chair in Precision Oncology and Cancer Prevention (POCP), Pan African Cancer Research Institute (PACRI), University of Pretoria, Pretoria 0001, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,4,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1186\/s41199-018-0037-5","article-title":"Nodal disease predicts recurrence whereas other traditional factors affect survival in a cohort of South African patients with differentiated thyroid carcinoma","volume":"3","author":"Robertson","year":"2018","journal-title":"Cancers Head Neck"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"6516035","DOI":"10.1155\/2018\/6516035","article-title":"Follicular Thyroid Carcinoma in a Country of Endemic Iodine Deficiency (1994\u20132013)","volume":"2018","author":"Der","year":"2018","journal-title":"J. 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