Mevalonate pathway activity as a determinant of radiation sensitivity in head and neck cancer.
Mevalonate pathway activity as a determinant of radiation sensitivity in head and neck cancer.
复制标题
甲羟戊酸途径活性是头颈癌辐射敏感性的决定因素。
DOI：
10.1002/1878-0261.12535
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发表时间：
2019
影响因子：
6.6
通讯作者：
Kron,StephenJ
中科院分区：
文献类型：
--
作者：
Ricco,Natalia;Flor,Amy;Wolfgeher,Don;Efimova,ElenaV;Ramamurthy,Aishwarya;Appelbe,OliverK;Brinkman,Jacqueline;Truman,AndrewW;Spiotto,MichaelT;Kron,StephenJ
放射耐药是头颈部鳞状细胞癌（HNSCC）治疗的主要障碍。在这里，我们报告了放疗和甲羟戊酸途径抑制剂（他汀类药物）联合治疗HNSCCs可能克服耐药性。蛋白质组学分析和放射敏感性HNSCCs的放射抗性比较揭示了甲羟戊酸生物合成途径的差异调节。与这一发现一致的是，匹伐他汀抑制甲羟戊酸途径使放射耐药SQ20B细胞对电离辐射敏感，并降低了它们的克隆潜能。总的来说，这项研究强化了甲羟戊酸途径是放射耐药HNSCCs的一个有希望的治疗靶点的观点。
Radioresistance is a major hurdle in the treatment of head and neck squamous cell carcinoma (HNSCC). Here, we report that concomitant treatment of HNSCCs with radiotherapy and mevalonate pathway inhibitors (statins) may overcome resistance. Proteomic profiling and comparison of radioresistant to radiosensitive HNSCCs revealed differential regulation of the mevalonate biosynthetic pathway. Consistent with this finding, inhibition of the mevalonate pathway by pitavastatin sensitized radioresistant SQ20B cells to ionizing radiation and reduced their clonogenic potential. Overall, this study reinforces the view that the mevalonate pathway is a promising therapeutic target in radioresistant HNSCCs.