Maione Paolo, Sacco Paola Claudia, Sgambato Assunta, Casaluce Francesca, Rossi Antonio, Gridelli Cesare
Division of Medical Oncology, 'S. G. Moscati' Hospital, Contrada Amoretta, Avellino, 83100, Italy.
Division of Medical Oncology, 'S. G. Moscati' Hospital, Avellino, Italy.
Ther Adv Med Oncol. 2015 Sep;7(5):263-73. doi: 10.1177/1758834015595048.
The discovery that a number of aberrant tumorigenic processes and signal transduction pathways are mediated by druggable protein kinases has led to a revolutionary change in nonsmall cell lung cancer (NSCLC) treatment. Epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) are the targets of several tyrosine kinase inhibitors (TKIs), some of them approved for treatment and others currently in clinical development. First-generation agents offer, in target populations, a substantial improvement of outcomes compared with standard chemotherapy in the treatment of advanced NSCLC. Unfortunately, drug resistance develops after initial benefit through a variety of mechanisms. Novel generation EGFR and ALK inhibitors are currently in advanced clinical development and are producing encouraging results in patients with acquired resistance to previous generation agents. The search for new drugs or strategies to overcome the TKI resistance in patients with EGFR mutations or ALK rearrangements is to be considered a priority for the improvement of outcomes in the treatment of advanced NSCLC.
一些异常的肿瘤发生过程和信号转导途径由可成药的蛋白激酶介导，这一发现给非小细胞肺癌（NSCLC）治疗带来了革命性变化。表皮生长因子受体（EGFR）和间变性淋巴瘤激酶（ALK）是几种酪氨酸激酶抑制剂（TKIs）的靶点，其中一些已获批用于治疗，另一些目前正处于临床开发阶段。在晚期NSCLC治疗中，第一代药物在目标人群中与标准化疗相比能显著改善治疗结果。不幸的是，在初始获益后会通过多种机制产生耐药性。新一代EGFR和ALK抑制剂目前正处于临床开发后期，在对前一代药物产生获得性耐药的患者中取得了令人鼓舞的结果。对于改善晚期NSCLC治疗结果而言，寻找克服EGFR突变或ALK重排患者中TKI耐药性的新药或策略应被视为优先事项。
