Methods for Overcoming Chemoresistance in Head and Neck Squamous Cell Carcinoma: Keeping the Focus on Cancer Stem Cells, a Systematic Review

According to the “cancer stem cell” (CSCs) theory, tumors are a diverse and expanding group of malignant cells that originate from a small number of CSCs. Despite treatment, these cells can still become active and proliferate, which can result in distant metastasis and local recurrences. A new paradigm in cancer treatment involves targeting both CSCs and the cancer cells in a tumor. This review aims to examine the literature on methods published to overcome chemoresistance due to the presence of CSCs in head and neck cancers. The review was registered with PROSPERO (ID# CRD42024512809). After Pub Med, Scopus, and WoS database searches, 31 relevant articles on oral squamous cell carcinoma (OSCC) were selected. Compounds that increased chemosensitivity by targeting CSCs in head and neck squamous cell carcinoma (HNSCC) were divided into (1) natural products, (2) adjuvant molecules to traditional chemotherapy, and (3) CSCs targeting patient-specific fresh biopsies for functional precision medicine.