The University of Texas M D Anderson Cancer Center, Department of Breast Medical Oncology, Houston, TX 77030-3721, USA.
J Clin Oncol. 2010 Jul 10;28(20):3366-79. doi: 10.1200/JCO.2009.25.4011. Epub 2010 Jun 7.
Increased understanding of the molecular events involved in cancer development has led to the identification of a large number of novel targets and, in parallel, to the development of multiple approaches to anticancer therapy. Targeted therapy focuses on specific molecules in the malignant cell signal transduction machinery, including crucial molecules involved in cell invasion, metastasis, apoptosis, cell-cycle control, and tumor-related angiogenesis. In breast cancer, two new targeted agents have recently been approved: lapatinib, directed against the human epidermal growth factor receptor 2 (HER2); and bevacizumab, directed against vascular endothelial growth factor (VEGF). Multiple other targeted agents are under evaluation in clinical trials, including inhibitors of the epidermal growth factor receptor (EGFR), dual EGFR and HER2 inhibitors, other VEGF or VEGF-receptor inhibitors, and agents that alter crucial signaling pathways, such as RAS/MEK/ERK; phosphatidylinositol-3-kinase/Akt/ mammalian target of rapamycin; insulin-like growth factor/insulin-like growth factor receptor; poly (ADP-ribose) polymerase 1; and others. In this review, we present the most promising studies of these new targeted therapies and novel combinations of targeted therapies with traditional cytotoxic agents.
对癌症发生过程中涉及的分子事件的深入了解，已导致大量新的靶标被识别，同时也并行发展出多种抗癌治疗方法。靶向治疗侧重于恶性细胞信号转导机制中的特定分子，包括参与细胞浸润、转移、凋亡、细胞周期控制和肿瘤相关血管生成的关键分子。在乳腺癌中，最近有两种新的靶向药物获得批准：针对人表皮生长因子受体 2（HER2）的拉帕替尼（lapatinib）和针对血管内皮生长因子（VEGF）的贝伐单抗（bevacizumab）。还有多种其他靶向药物正在临床试验中进行评估，包括表皮生长因子受体（EGFR）抑制剂、EGFR 和 HER2 双重抑制剂、其他 VEGF 或 VEGF 受体抑制剂，以及改变关键信号通路的药物，如 RAS/MEK/ERK、磷脂酰肌醇-3-激酶/Akt/哺乳动物雷帕霉素靶蛋白、胰岛素样生长因子/胰岛素样生长因子受体、多聚（ADP-核糖）聚合酶 1 等。在这篇综述中，我们介绍了这些新的靶向治疗方法以及靶向治疗与传统细胞毒性药物联合应用的最有前途的研究。
