1 Department of Medical Oncology, Chris O'Brien Lifehouse, Camperdown, NSW, Australia ; 2 Department of Medical Oncology, Macarthur Cancer Therapy Centre, Campbelltown, NSW, Australia.
Transl Lung Cancer Res. 2015 Apr;4(2):165-76. doi: 10.3978/j.issn.2218-6751.2015.01.04.
Non-small cell lung cancer (NSCLC) is a devastating disease with poor prognosis. Systemic chemotherapy has been the mainstay of treatment in advanced disease for many decades. Personalized targeted therapy such as epidermal growth factor receptor tyrosine kinase inhibitors (EGFR TKIs) and crizotinib has significantly changed the treatment paradigm in NSCLC. The future success of development of molecular targeted therapy relies on the understanding of signal transduction pathways. The PI3K-Akt-mTOR pathway is commonly deregulated in human malignancy including NSCLC. Therefore, this pathway is a target for many therapeutic developments. This review will provide an overview of PI3K-Akt-mTOR signaling pathway, genetic alterations activating the pathway and clinical therapeutic development of pathway inhibitors.
非小细胞肺癌(NSCLC)是一种预后不良的毁灭性疾病。几十年来,系统化疗一直是晚期疾病的主要治疗方法。表皮生长因子受体酪氨酸激酶抑制剂(EGFR TKIs)和克唑替尼等个性化靶向治疗已显著改变了 NSCLC 的治疗模式。分子靶向治疗的未来成功取决于对信号转导途径的理解。PI3K-Akt-mTOR 途径在包括 NSCLC 在内的人类恶性肿瘤中通常失调。因此,该途径是许多治疗开发的目标。本文综述了 PI3K-Akt-mTOR 信号通路、激活该通路的遗传改变以及通路抑制剂的临床治疗进展。