School of Basic Pharmaceutical and Toxicological Sciences, College of Pharmacy, University of Louisiana at Monroe, Monroe LA 71201, United States.
Curr Med Chem. 2020;27(32):5274-5316. doi: 10.2174/0929867326666190222183219.
Eighty-five percent of patients with lung cancer present with Non-small Cell Lung Cancer (NSCLC). Targeted therapy approaches are promising treatments for lung cancer. However, despite the development of targeted therapies using Tyrosine Kinase Inhibitors (TKI) as well as monoclonal antibodies, the five-year relative survival rate for lung cancer patients is still only 18%, and patients inevitably become resistant to therapy. Mutations in Kirsten Ras Sarcoma viral homolog (KRAS) and epidermal growth factor receptor (EGFR) are the two most common genetic events in lung adenocarcinoma; they account for 25% and 20% of cases, respectively. Anaplastic Lymphoma Kinase (ALK) is a transmembrane receptor tyrosine kinase, and ALK rearrangements are responsible for 3-7% of NSCLC, predominantly of the adenocarcinoma subtype, and occur in a mutually exclusive manner with KRAS and EGFR mutations. Among drug-resistant NSCLC patients, nearly half exhibit the T790M mutation in exon 20 of EGFR. This review focuses on some basic aspects of molecules involved in NSCLC, the development of resistance to treatments in NSCLC, and advances in lung cancer therapy in the past ten years. Some recent developments such as PD-1-PD-L1 checkpoint-based immunotherapy for NSCLC are also covered.
85%的肺癌患者患有非小细胞肺癌（NSCLC）。靶向治疗方法是治疗肺癌的有前途的治疗方法。然而，尽管使用酪氨酸激酶抑制剂（TKI）和单克隆抗体开发了靶向疗法，但肺癌患者的五年相对生存率仍仅为 18%，并且患者不可避免地对治疗产生耐药性。Kirsten Ras Sarcoma viral homolog (KRAS) 和表皮生长因子受体 (EGFR) 的突变是肺腺癌中最常见的两种遗传事件；它们分别占病例的 25%和 20%。间变性淋巴瘤激酶（ALK）是一种跨膜受体酪氨酸激酶，ALK 重排占 NSCLC 的 3-7%，主要为腺癌亚型，与 KRAS 和 EGFR 突变相互排斥。在耐药性 NSCLC 患者中，近一半的患者在 EGFR 的外显子 20 中表现出 T790M 突变。这篇综述重点介绍了 NSCLC 中涉及的一些分子的一些基本方面、NSCLC 治疗耐药性的发展以及过去十年中肺癌治疗的进展。还涵盖了一些最近的进展，如针对 NSCLC 的 PD-1-PD-L1 检查点免疫疗法。
