Bustamante Alvarez Jean G, González-Cao María, Karachaliou Niki, Santarpia Mariacarmela, Viteri Santiago, Teixidó Cristina, Rosell Rafael
1 Albert Einstein Medical Center, Philadelphia 19141, USA ; 2 Translational Cancer Research Unit, Instituto Oncológico Dr Rosell, Quirón Dexeus University Hospital, Barcelona 08028, Spain ; 3 Medical Oncology Unit, Human Pathology Department, University of Messina, Messina 98100, Italy ; 4 Pangaea Biotech S.L, Barcelona 08028, Spain ; 5 Cancer Biology & Precision Medicine Program, Catalan Institute of Oncology, Germans Trias i Pujol Health Sciences Institute and Hospital, Campus Can Ruti, Badalona, Barcelona 08916, Spain ; 6 Fundación Molecular Oncology Research, Barcelona 08028, Spain.
Cancer Biol Med. 2015 Sep;12(3):209-22. doi: 10.7497/j.issn.2095-3941.2015.0032.
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 antibody, 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.
随着时间的推移,已经开发出了多种治疗肺癌的方法,包括化疗、放疗以及针对激活突变的靶向治疗。最近,对免疫系统在肿瘤控制中作用的深入了解为实施不同策略以增强针对癌细胞的免疫反应打开了多扇大门。众所周知,肿瘤细胞通过多种机制逃避免疫反应。针对T细胞上的检查点抑制剂程序性细胞死亡蛋白1(PD-1)及其配体(PD-L1)开发的单克隆抗体,已在癌症患者中显示出高活性且反应持久。抗PD-1抑制剂纳武单抗最近已被批准用于治疗鳞状细胞肺癌患者,这是基于一项III期试验中显示的生存优势。另一种抗PD-1抗体帕博利珠单抗已获得FDA突破性疗法认定,用于治疗非小细胞肺癌(NSCLC),这一认定得到了一项I期试验数据的支持。在NSCLC中使用抗PD-1/PD-L1抗体的临床试验已证明耐受性和活性都非常好,缓解率约为20%,中位缓解持续时间为18个月。