Zhu Chennianci, Zhuang Weihao, Chen Limin, Yang Wenyu, Ou Wen-Bin
Zhejiang Provincial Key Laboratory of Silkworm Bioreactor and Biomedicine, College of Life Sciences and Medicine, Zhejiang Sci-Tech University, Hangzhou 310018, China.
Transl Lung Cancer Res. 2020 Feb;9(1):111-138. doi: 10.21037/tlcr.2020.01.09.
Non-small-cell lung cancer (NSCLC), a main subtype of lung cancer, is one of the most common causes of cancer death in men and women worldwide. Circulating tumor DNA (ctDNA), tyrosine kinase inhibitors (TKIs) and immunotherapy have revolutionized both our understanding of NSCLC, from its diagnosis to targeted NSCLC therapies, and its treatment. ctDNA quantification confers convenience and precision to clinical decision making. Furthermore, the implementation of TKI-based targeted therapy and immunotherapy has significantly improved NSCLC patient quality of life. This review provides an update on the methods of ctDNA detection and its impact on therapeutic strategies; therapies that target epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) using TKIs such as osimertinib and lorlatinib; the rise of various resistant mechanisms; and the control of programmed cell death-1 (PD-1), programmed cell death ligand-1 (PD-L1), and cytotoxic T-lymphocyte antigen-4 (CTLA-4) by immune checkpoint inhibitors (ICIs) in immunotherapy; blood tumor mutational burden (bTMB) calculated by ctDNA assay as a novel biomarker for immunotherapy. However, NSCLC patients still face many challenges. Further studies and trials are needed to develop more effective drugs or therapies to treat NSCLC.
非小细胞肺癌（NSCLC）是肺癌的主要亚型，是全球男性和女性癌症死亡的最常见原因之一。循环肿瘤DNA（ctDNA）、酪氨酸激酶抑制剂（TKIs）和免疫疗法彻底改变了我们对NSCLC的认识，从其诊断到靶向NSCLC治疗及其治疗方法。ctDNA定量为临床决策提供了便利和精准性。此外，基于TKI的靶向治疗和免疫疗法的实施显著提高了NSCLC患者的生活质量。本综述提供了关于ctDNA检测方法及其对治疗策略影响的最新信息；使用奥希替尼和劳拉替尼等TKI靶向表皮生长因子受体（EGFR）和间变性淋巴瘤激酶（ALK）的疗法；各种耐药机制的出现；以及免疫疗法中免疫检查点抑制剂（ICIs）对程序性细胞死亡蛋白1（PD-1）、程序性细胞死亡配体1（PD-L1）和细胞毒性T淋巴细胞抗原4（CTLA-4）的调控；通过ctDNA检测计算的血液肿瘤突变负荷（bTMB）作为免疫疗法的一种新型生物标志物。然而，NSCLC患者仍面临许多挑战。需要进一步的研究和试验来开发更有效的药物或疗法来治疗NSCLC。
