蛋白酶体抑制剂在非小细胞肺癌靶向治疗中的研究进展

Research progress of proteasome inhibition in targeted therapies for non-small cell lung cancer

肺癌是全球癌症死亡的首要原因,其中非小细胞肺癌（non-small cell lung cancer,NSCLC）约占肺癌80%～85%.目前临床的一线治疗方案是以铂为基础的联合化疗,但晚期NSCLC患者预后仍然较差,中位生存时间为（9.5±1.5）个月,1年生存率仅为30%.因此,NSCLC的治疗目前仍是极需满足的临床需要.泛素蛋白酶体系统（ubiquitin-proteasome system,UPS）是肿瘤细胞增殖和存活的关键,因此UPS已成为非常具有吸引力的抗癌治疗新方法.文中将评估UPS与不同类型肿瘤生长抑制的关联性,探讨蛋白酶体抑制剂在NSCLC靶向治疗中的作用机制,现就文献中关于使用蛋白酶体抑制剂单药或联合化疗来治疗肺癌患者的研究成果做一个最新的回顾.

Lung cancer is the leading cause of cancer-related deaths globally. Non-small cell lung cancer （NSCLC） accounts for approximately ranged from 80% to 85% of all cases of lung cancer. Combination chemotherapy, usually platinum-based, is currently the first-line therapy of choice, however, the prognosis for patients with advanced NSCLC remains poor with a median survival time of （9.5±1.5） months and a 1-year survival rate of 30%. The treatment of NSCLC is therefore a major unmet need. There is now a great interest to find targeted therapies that can be effective not only to palliate lung cancer or decrease treatment-related toxicity, but also give hope to cure these patients. It is already well known that the ubiquitin-proteasome system is critical for the proliferation and survival of cancer cells; thus, proteosome inhibition has become a very attractive anticancer therapy. Here, this paper evaluates the correlation of ubiquitin-proteasome system with different types of tumor growth inhibition, explores the mechanism of proteasome inhibition in targeted therapies for non-small cell lung cancer, then make a state-of-the-art review based on the available literature regarding the use of proteosome inhibition as a single agent or in combination with chemotherapy in patients with lung cancer.