Abstract
BACKGROUND: Cervical cancer remains a leading cause of cancer-related mortality among women globally. Persistent infection with high-risk human papillomavirus drives cervical carcinogenesis, and treatment outcomes are frequently challenged by metastasis and chemoresistance. The transmembrane glycoprotein cluster of differentiation 44 (CD44), a marker associated with cancer stem cells (CSCs), has emerged as a critical mediator of both processes in cervical cancer. OBJECTIVE: This review aims to critically evaluate current evidence on the role of CD44 in cervical cancer progression, metastasis, and treatment resistance. It also explores the potential of resveratrol, a naturally occurring polyphenol with known anticancer properties, as a chemo-sensitizing agent to carboplatin therapy. METHODS: A comprehensive review of the literature was conducted using databases such as PubMed, Google Scholar, and Scopus to identify studies that investigate CD44-mediated mechanisms in cervical cancer, as well as the modulatory and mechanistic effects of resveratrol on CD44 and chemoresistance across various cancer types. RESULTS: CD44 has been consistently implicated in promoting drug resistance, epithelial-to-mesenchymal transition (EMT), and stemness in cervical cancer. Resveratrol has demonstrated antimetastatic and chemo-sensitizing effects in several malignancies, such as colorectal and breast cancers, often through modulation of CD44 and associated pathways. However, direct evidence in cervical cancer remains limited. CONCLUSION: Current findings suggest a promising therapeutic avenue for combining resveratrol with carboplatin to overcome CD44-mediated treatment resistance and metastasis in cervical cancer. Nonetheless, further cervical-specific studies are needed to validate this approach. A clearer understanding of this relationship may facilitate lower chemotherapy dosing, reduced toxicity, and improved clinical outcomes.