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Advances in immunotherapy for treatment of lung cancer 被引量:23
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作者 Jean G.Bustamante Alvarez María González-Cao +4 位作者 Niki Karachaliou Mariacarmela Santarpia Santiago Viteri Cristina Teixidó Rafael Rosell 《Cancer Biology & Medicine》 SCIE CAS CSCD 2015年第3期209-222,共14页
Different approaches for treating lung cancer have been developed over time, including chemotherapy, radiotherapy and targeted therapies against activating mutations. Lately, better understanding of the role of the im... Different approaches for treating lung cancer have been developed over time, including chemotherapy, radiotherapy and targeted therapies against activating mutations. Lately, better understanding of the role of the immunological system in tumor control has opened multiple doors to implement different strategies to enhance immune response against cancer cells. It is known that tumor cells elude immune response by several mechanisms. The development of monoclonal antibodies against the checkpoint inhibitor programmed cell death protein 1 (PD-1) and its ligand (PD-L1), on T cells, has led to high activity in cancer patients with long lasting responses. Nivolumab, an anti PD-1 inhibitor, has been recently approved for the treatment of squamous cell lung cancer patients, given the survival advantage demonstrated in a phase III trial. Pembrolizumab~ another anti PD-1 antibod)5 has received FDA breakthrough therapy designation for treatment of non-small cell lung cancer (NSCLC), supported by data from a phase I trial. Clinical trials with anti PD-1/PD-L1 antibodies in NSCLC have demonstrated very good tolerability and activity, with response rates around 20% and a median duration of response of 18 months. 展开更多
关键词 Cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) immune checkpoint inhibitors lung cancer programmed celldeath protein ligand-1 (PD-L1) programmed cell death protein i (PD-1)
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ALK和ROS1:肺癌治疗的联合靶点
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作者 Raimon Puig de la Bellacasa Niki Karachaliou +5 位作者 Roger Estrada-Tejedor Jordi Teixidó Carlota Costa José I.Borrell 吴冠楠(译) 宋勇(审校) 《临床与病理杂志》 CAS 2014年第1期1-14,共14页
间变性淋巴瘤激酶(anaplastic lymphoma kinase,ALK)基因重排可见于包括非小细胞肺癌(non small cell lung cancer,NSCLC)在内的多种恶性肿瘤中。ALK融合基因使激酶具有异常活性,而野生型ALK激酶域突变也可使它被激活。ALK基因重排使得N... 间变性淋巴瘤激酶(anaplastic lymphoma kinase,ALK)基因重排可见于包括非小细胞肺癌(non small cell lung cancer,NSCLC)在内的多种恶性肿瘤中。ALK融合基因使激酶具有异常活性,而野生型ALK激酶域突变也可使它被激活。ALK基因重排使得NSCLC中出现了新的分子亚型,该亚型对ALK抑制剂高度耐药。克唑替尼(crizotinib)是一个口服小分子ATP模拟化合物,它最初作为MET抑制剂被开发,随后被发现具有抗ALK活性的脱靶效应(off target),并被美国FDA批准用于治疗ALK阳性的NSCLC患者。近来在NSCLC患者中还发现了ROS1受体酪氨酸激酶染色体重排,而克唑替尼正处于治疗该分子亚型NSCLC患者的临床试验中。任何计算机辅助药物设计都是依赖其分子结构和配体的药物设计方法,每种方法的详细信息中均应重点强调利用这二者,以开发多靶点小分子激酶抑制剂。此类多靶点小分子激酶抑制剂均可对ROS1和ALK重排的NSCLC有抑制增殖作用。因此,本综述重点强调了关于靶向这些激酶的重要性,以及在优化出效能更佳、选择性更强的ROS1和ALK激酶抑制剂中所取得的进步。 展开更多
关键词 间变性淋巴瘤激酶 药物设计 激酶抑制剂 非小细胞肺癌 ROS1
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