Prabhu Venugopal Vinod, Devaraj Niranjali
Department of Biochemistry, University of Madras, Guindy campus, Chennai-600025, Tamil Nadu, India.
J Environ Pathol Toxicol Oncol. 2017;36(2):151-158. doi: 10.1615/JEnvironPatholToxicolOncol.2017018341.
Lung cancer is responsible for 1.6 million deaths. Approximately 80%-85% of lung cancers are of the non-small-cell variety, which includes squamous cell carcinoma, adenocarcinoma, and large-cell carcinoma. Knowing the stage of cancer progression is a requisite for determining which management approach-surgery, chemotherapy, radiotherapy, and/or immunotherapy-is optimal. Targeted therapeutic approaches with antiangiogenic monoclonal antibodies or tyrosine kinase inhibitors are one option if tumors harbor oncogene mutations. Another, newer approach is directed against cancer-specific molecules and signaling pathways and thus has more limited nonspecific toxicities. This approach targets the epidermal growth factor receptor (EGFR, HER-1/ErbB1), a receptor tyrosine kinase of the ErbB family, which consists of four closely related receptors: HER-1/ErbB1, HER-2/neu/ErbB2, HER-3/ErbB3, and HER-4/ErbB4. Because EGFR is expressed at high levels on the surface of some cancer cells, it has been recognized as an effective anticancer target. EGFR-targeted therapies include monoclonal antibodies (mAbs) and small-molecule tyrosine kinase inhibitors. Tyrosine kinases are an especially important target because they play an important role in the modulation of growth factor signaling. This review highlights various classes of synthetically derived molecules that have been reported in the last few years as potential EGFR-TK inhibitors (TKIs) and their targeted therapies in NSCLC, along with effective strategies for overcoming EGFR-TKI resistance and efforts to develop a novel potent EGFR-TKI as an efficient target of NSCLC treatment in the foreseeable future.
肺癌导致160万人死亡。大约80%-85%的肺癌属于非小细胞类型，包括鳞状细胞癌、腺癌和大细胞癌。了解癌症进展阶段是确定哪种治疗方法——手术、化疗、放疗和/或免疫治疗——最为合适的必要条件。如果肿瘤存在致癌基因突变，使用抗血管生成单克隆抗体或酪氨酸激酶抑制剂的靶向治疗方法是一种选择。另一种更新的方法是针对癌症特异性分子和信号通路，因此非特异性毒性更有限。这种方法靶向表皮生长因子受体（EGFR，HER-1/ErbB1），它是ErbB家族的一种受体酪氨酸激酶，该家族由四种密切相关的受体组成：HER-1/ErbB1、HER-2/neu/ErbB2、HER-3/ErbB3和HER-4/ErbB4。由于EGFR在某些癌细胞表面高水平表达，它已被认为是一个有效的抗癌靶点。EGFR靶向治疗包括单克隆抗体（mAbs）和小分子酪氨酸激酶抑制剂。酪氨酸激酶是一个特别重要的靶点，因为它们在生长因子信号调节中起重要作用。本综述重点介绍了过去几年报道的各类合成衍生分子，它们作为潜在的EGFR酪氨酸激酶抑制剂（TKIs）及其在非小细胞肺癌中的靶向治疗，以及克服EGFR-TKI耐药性的有效策略，以及在可预见的未来开发新型强效EGFR-TKI作为非小细胞肺癌治疗有效靶点的努力。
