Targeting the IRAK1–S100A9 Axis Overcomes Resistance to Paclitaxel in Nasopharyngeal Carcinoma

Abstract Novel strategies to treat late-stage nasopharyngeal carcinoma that often develop resistance chemotherapy remains an unmet clinical demand. In this study, we identify the multi-kinase inhibitor pacritinib as capable of resensitizing response paclitaxel in acquired model. Transcriptome analysis paclitaxel-sensitive and -resistant cell lines, well chemorefractory samples, identified S100A9 top candidate gene suppressed by whose overexpression was significantly associated with poor outcome. Moreover, both paclitaxel-resistant cells relapsed/metastatic samples exhibited increased IRAK1 phosphorylation demonstrated could abolish suppress expression. Functional studies vitro vivo models showed genetic or pharmacologic blockade overcame paclitaxel, combined treatment superior antitumor effect. Together, these findings demonstrate important role for IRAK1–S100A9 axis mediating paclitaxel. Furthermore, targeting may provide a novel therapeutic strategy overcome chemoresistance carcinoma. Significance: Deregulation correlates prognosis, contributes carcinoma, can be targeted