Publication Date
2-19-2024
Journal
BMC Cancer
DOI
10.1186/s12885-024-11892-9
PMID
38373988
PMCID
PMC10875868
PubMedCentral® Posted Date
2-19-2024
PubMedCentral® Full Text Version
Post-print
Published Open-Access
yes
Keywords
Humans, Antineoplastic Agents, Apoptosis, Cell Line, Tumor, Cisplatin, Drug Resistance, Neoplasm, Head and Neck Neoplasms, Squamous Cell Carcinoma of Head and Neck, Ribosomal Protein S6 Kinases, 90-kDa, Anoctamin-1
Abstract
Head and neck squamous cell carcinoma (HNSCC) constitutes one of the most common types of human cancers and often metastasizes to lymph nodes. Platinum-based chemotherapeutic drugs are commonly used for treatment of a wide range of cancers, including HNSCC. Its mode of action relies on its ability to impede DNA repair mechanisms, inducing apoptosis in cancer cells. However, due to acquired resistance and toxic side-effects, researchers have been focusing on developing novel combinational therapeutic strategies to overcome cisplatin resistance. In the current study, we identified p90RSK, an ERK1/2 downstream target, as a key mediator and a targetable signaling node against cisplatin resistance. Our results strongly support the role of p90RSK in cisplatin resistance and identify the combination of p90RSK inhibitor, BI-D1870, with cisplatin as a novel therapeutic strategy to overcome cisplatin resistance. In addition, we have identified TMEM16A expression as a potential upstream regulator of p90RSK through the ERK pathway and a biomarker of response to p90RSK targeted therapy in the context of cisplatin resistance.