Premiere Oncology, 2020 Santa Monica Boulevard, Suite 600, Santa Monica, California 90404, USA.
Oncologist. 2010;15(3):216-35. doi: 10.1634/theoncologist.2009-0145. Epub 2010 Mar 3.
Greater understanding of the underlying etiology and biology of breast cancer is enabling the clinical development of targeted therapies for metastatic breast cancer (MBC). Following the successful introduction of trastuzumab, the first human epidermal growth factor receptor (HER) biologically targeted therapy to become widely used in MBC patients, other agents have been developed. Novel agents include monoclonal antibodies such as pertuzumab, which bind to receptors on the cell surface, and tyrosine kinase inhibitors (TKIs) such as lapatinib, which target intracellular pathways such as that of the epidermal growth factor receptor. There is also growing clinical experience with antiangiogenic agents, particularly in combination with chemotherapy. These include the monoclonal antibody bevacizumab, which targets vascular endothelial growth factor receptor, and multitargeted TKIs with antiangiogenic and antiproliferative activities, such as sunitinib. Combination treatment with multiple agents targeting both the HER family and angiogenic pathways (e.g., trastuzumab plus bevacizumab) is also showing activity in the clinical setting. Despite recent advances, there are unanswered questions regarding the management of MBC with targeted agents. Future studies are necessary to determine the optimal combinations, doses, and schedules required to maximize clinical activity while minimizing toxicity. Despite the temptation to use a targeted agent in all patients, identification of patient subgroups most likely to benefit must be a key goal and will be critical to the successful future use of these treatments. The aim of this review is to summarize some of the key signaling pathways involved in tumor progression and some of the novel therapies that are in development for MBC.
对乳腺癌潜在病因和生物学的更深入了解，使针对转移性乳腺癌（MBC）的靶向治疗的临床开发成为可能。继曲妥珠单抗（第一个广泛用于 MBC 患者的人表皮生长因子受体（HER）生物靶向治疗药物）成功上市后，其他药物也相继问世。新型药物包括与细胞表面受体结合的单克隆抗体，如帕妥珠单抗，以及针对细胞内途径（如表皮生长因子受体途径）的酪氨酸激酶抑制剂（TKI），如拉帕替尼。抗血管生成药物也有越来越多的临床经验，特别是与化疗联合使用。这些药物包括针对血管内皮生长因子受体的单克隆抗体贝伐珠单抗，以及具有抗血管生成和抗增殖活性的多靶点 TKI，如舒尼替尼。针对 HER 家族和血管生成途径的多种靶向药物联合治疗（如曲妥珠单抗联合贝伐珠单抗）在临床实践中也显示出疗效。尽管最近取得了进展，但针对靶向药物治疗 MBC 的管理仍存在一些尚未解决的问题。未来的研究需要确定最佳组合、剂量和方案，以最大限度地提高临床疗效，同时最小化毒性。尽管有使用靶向药物治疗所有患者的诱惑，但确定最有可能受益的患者亚组必须是一个关键目标，这对于这些治疗方法的成功未来应用至关重要。本文旨在总结肿瘤进展中涉及的一些关键信号通路和正在开发用于 MBC 的一些新型治疗方法。
