Overcoming Resistance to EGFR inhibitor in Head and Neck Squamous Cell Carcinoma

尽管头颈部鳞状细胞癌(HNSCC)患者的治疗取得了进展，但患者的生存率并未得到显著提高。因此，寻找潜在的替代疗法是令人鼓舞的。在目前的研究中，我们检测了鱼藤素，一种来自非洲植物丝光藤鱼藤素对头颈部鳞状细胞癌细胞株的影响。结果表明，鱼腥草素通过抑制AKT的结构性激活和EGF刺激的AKT激活而诱导细胞凋亡。我们进一步证明鱼藤素抑制IGF1R-AKT通路，EGFR抗体西妥昔单抗适用于HNSCC的治疗。然而，除了EGFR-AKT途径外，西妥昔单抗对HNSCC耐药的机制可能是IGF1R-AKT信号转导。因此，这些结果提示鱼藤素可以克服HNSCC对EGFR抑制剂的耐药性。还需要进一步的工作。

Despite advances in the management of head and neck squamous cell carcinoma (HNSCC) patients, the survival has not been significantly improved. Therefore, the search for potential alterative therapies is encouraging. In the current study, we examined the effect of deguelin, a rotenoid from the African plant Mundulea sericea on head and neck squamous cell carcinoma cell lines. The results demonstrated that deguelin induced apoptosis by inhibiting constitutive and EGF-stimulated AKT activation. We further demonstrated that deguelin inhibited IGF1R-AKT pathway.Cetuximab, antibody of EGFR, is an applicable for HNSCC therapy. However, a mechanism of cetuximab resistance for HNSCC is thought to be IGF1R-AKT signaling in addition to EGFR-AKT pathway. Therefore, these results suggested that deguelin may overcome resistance to EGFR inhibitor in HNSCC. Further work is needed.