PI3K-AKT-mTOR信号通路中关键信号分子在中国黑色素瘤中的表达与变异情况

Recent studies have shown those two important signaling pathways in the growth and metastasis of melanoma, which included mitogen-activated protein kinase (MAPK) signaling pathway and the PI3K-AKT-mTOR signaling pathway. BRAF and CKIT are important molecular components in RAS-RAF-MEK-ERK signaling pathway of MAPK which have been fully investigated. Inhibitors targeted BARF or CKIT have been utilized in the treatment of related gene-mutation-harboring melanoma patients. The outcomes of the inhibitors showed more effective compared with conventional chemotherapy. Thus, the individual targeted therapy based on the signaling pathways has gradually become the primary treatment strategy for advanced melanoma. However, studies found that not all patients harbored with BRAF or CKIT gene mutations. The PI3K-AKT-mTOR signaling pathway may be a new breakthrough of the others without BRAF or CKIT gene mutations which has not been fully studied. This project intends to exam the expression and mutation of important factors in PI3K-AKT-mTOR signaling pathway in melanoma patients. It would provide valuable clues of reasonable and smart individual targeted therapy selection in melanoma patients once the correlation of these gene variants and melanoma clinical pathological features clarified.

黑色素瘤发生发展过程中有两个重要的信号通路：丝裂原活化蛋白激酶(MAPK)信号通路和PI3K-AKT-mTOR信号通路。其中对MAPK通路中RAS--RAF-MEK-ERK信号途径中的重要组成分子BRAF和CKIT研究较为充分，用BRAF和CKIT抑制剂来治疗相关基因变异患者的有效率和无进展生存均明显高于常规化疗，分子靶向治疗已逐渐成为晚期黑色素瘤的首要治疗策略。然而研究发现不是所有黑色素瘤患者都存在BRAF或CKIT变异，仍有半数患者找不到特定靶标和有效治疗方案，PI3K-AKT-mTOR这一重要信号通路有可能是新的突破点，而有关mTOR通路在中国黑色素瘤中活化及基因变异情况尚无报道。本课题拟对中国黑色素瘤PI3K-AKT-mTOR信号通路中重要分子进行基因变异检测，明确基因变异与黑色素瘤临床病理特征的关系，为未来临床选择合理的靶向药物提供有价值的线索。