Department of Internal Medicine, Affiliated Cancer Hospital of Zhengzhou University, Henan Cancer Hospital, 127 Dong Ming Road, Zhengzhou, 450008, China.
Department of Radiotherapy, Affiliated Cancer Hospital of Zhengzhou University, Henan Cancer Hospital, 127 Dong Ming Road, Zhengzhou, 450008, China.
J Hematol Oncol. 2021 Jan 5;14(1):1. doi: 10.1186/s13045-020-01025-7.
BRAF and KRAS are two key oncogenes in the RAS/RAF/MEK/MAPK signaling pathway. Concomitant mutations in both KRAS and BRAF genes have been identified in non-small cell lung cancer (NSCLC). They lead to the proliferation, differentiation, and apoptosis of tumor cells by activating the RAS/RAF/MEK/ERK signaling pathway. To date, agents that target RAS/RAF/MEK/ERK signaling pathway have been investigated in NSCLC patients harboring BRAF mutations. BRAF and MEK inhibitors have gained approval for the treatment of patients with NSCLC. According to the reported findings, the combination of MEK inhibitors with chemotherapy, immune checkpoint inhibitors, epidermal growth factor receptor-tyrosine kinase inhibitors or BRAF inhibitors is highly significant for improving clinical efficacy and causing delay in the occurrence of drug resistance. This review summarized the existing experimental results and presented ongoing clinical studies as well. However, further researches need to be conducted to indicate how we can combine other drugs with MEK inhibitors to significantly increase therapeutic effects on patients with lung cancer.
BRAF 和 KRAS 是 RAS/RAF/MEK/MAPK 信号通路中的两个关键致癌基因。非小细胞肺癌 (NSCLC) 中同时存在 KRAS 和 BRAF 基因突变。它们通过激活 RAS/RAF/MEK/ERK 信号通路，促进肿瘤细胞的增殖、分化和凋亡。迄今为止，针对携带 BRAF 突变的 NSCLC 患者的 RAS/RAF/MEK/ERK 信号通路靶向药物已经进行了研究。BRAF 和 MEK 抑制剂已被批准用于治疗 NSCLC 患者。根据已报道的研究结果，MEK 抑制剂联合化疗、免疫检查点抑制剂、表皮生长因子受体酪氨酸激酶抑制剂或 BRAF 抑制剂，可显著提高临床疗效，延缓耐药的发生。本综述总结了现有的实验结果，并介绍了正在进行的临床研究。然而，还需要进一步的研究来表明如何将其他药物与 MEK 抑制剂联合使用，以显著提高肺癌患者的治疗效果。
