Kahnert Kathrin, Kauffmann-Guerrero Diego, Huber Rudolf Maria
Department of Internal Medicine V, University of Munich, Comprehensive Pneumology Center, German Center for Lung Research, Munich, Germany.
Department of Internal Medicine V, University of Munich, Comprehensive Pneumology Center, German Center for Lung Research, Munich, Germany.
Clin Lung Cancer. 2016 Sep;17(5):325-333. doi: 10.1016/j.cllc.2016.05.014. Epub 2016 Jun 8.
Worldwide, the total number of diagnosed lung cancer cases amounts to 1.8 million every year. Small-cell lung cancer (SCLC) accounts for about 15% to 17% of all diagnosed lung cancers. Despite all progress made in the field of non-small-cell lung cancer, the prognosis and therapeutic options in SCLC are still limited. The resistance of SCLC to conventional therapy as well as its high recurrence rate can be attributed to the heterogeneous genetic structure of SCLC; however, a targeted therapy approach to SCLC may build on this very heterogeneous genetic structure. SCLC is by now a well-characterized cancer with various genetic alterations; for example, mutations in tumor suppressor genes TP53 and RB1, alterations in chromosome 3p, JAK2, FGFR1, and MYC genes were discovered. Based on these findings, various treatment options (eg, aurora kinase inhibitors, PARP inhibition, immune checkpoint inhibition and vaccine therapy) are currently evaluated with the goal of determining their clinical effectiveness. In this article, we review the existing knowledge of SCLC genetics and the current treatment standards and highlight new approaches of immunotherapy and other targeted therapies, which may yield new treatment options and improve the outcome of patients with SCLC.
在全球范围内,每年确诊的肺癌病例总数达180万例。小细胞肺癌(SCLC)约占所有确诊肺癌病例的15%至17%。尽管在非小细胞肺癌领域取得了诸多进展,但SCLC的预后和治疗选择仍然有限。SCLC对传统疗法的耐药性及其高复发率可归因于SCLC的异质性基因结构;然而,针对SCLC的靶向治疗方法可能正是基于这种非常异质的基因结构。目前,SCLC是一种具有各种基因改变的特征明确的癌症;例如,发现了肿瘤抑制基因TP53和RB1的突变、3号染色体短臂、JAK2、FGFR1和MYC基因的改变。基于这些发现,目前正在评估各种治疗选择(如极光激酶抑制剂、PARP抑制、免疫检查点抑制和疫苗疗法),目的是确定它们的临床疗效。在本文中,我们回顾了SCLC遗传学的现有知识和当前的治疗标准,并重点介绍了免疫疗法和其他靶向疗法的新方法,这些方法可能会产生新的治疗选择并改善SCLC患者的治疗结果。