Work

Decoding the role of cancer-associated fibroblasts in cisplatin resistance of head and neck squamous cell carcinoma

Year: 2026

Type: review

Abstract: Cisplatin remains the primary chemotherapy drug for the treatment of head and neck squamous cell carcinoma (HNSCC). However, acquired resistance significantly limits its clinical application, contributing to treatment failure and a poor patient prognosis. Cancer-associated fibroblasts (CAFs) in the tumor microenvironment influence HNSCC sensitivity to cisplatin by modulating tumor cell responsiveness to treatment via paracrine signaling. CAFs impede deep penetration into tumors by remodeling the extracellular matrix (ECM). Various subtypes of cisplatin-resistant CAFs have been identified in HNSCC. Potential compounds targeting these subtypes could enhance cisplatin sensitivity. Simulation of the dynamic tumor microenvironment remains limited in research, hindering clinical translation. Bioinformatics has shifted research into cisplatin resistance in HNSCC. Single-cell sequencing and spatiotemporal transcriptomics could analyze the molecular profiles of CAFs that promote drug resistance in greater depth, potentially facilitating the development of highly targeted drugs and effective combination therapy strategies to overcome cisplatin resistance in HNSCCs.

Source: iScience

DOI: 10.1016/j.isci.2026.117696