Targeting signal transduction pathways in metastatic breast cancer: a comprehensive review.
Targeting signal transduction pathways in metastatic breast cancer: a comprehensive review.
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DOI：
10.1634/theoncologist.2009-0145
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发表时间：
2010
期刊：
影响因子：
--
通讯作者：
Chap L
中科院分区：
文献类型：
--
作者：
Rosen LS;Ashurst HL;Chap L
这篇综述总结了肿瘤进展中涉及的一些关键信号通路以及一些正在开发的用于治疗转移性乳腺癌患者的新疗法。对乳腺癌潜在病因学和生物学的深入了解有助于转移性乳腺癌 (MBC) 靶向治疗的临床开发。继曲妥珠单抗（第一种人类表皮生长因子受体（HER）生物靶向疗法）成功引入并广泛应用于 MBC 患者之后，其他药物也被开发出来。新型药物包括单克隆抗体，如帕妥珠单抗，它与细胞表面的受体结合，以及酪氨酸激酶抑制剂（TKI），如拉帕替尼，其靶向细胞内途径，如表皮生长因子受体的途径。抗血管生成药物的临床经验也不断增加，特别是与化疗联合使用。其中包括针对血管内皮生长因子受体的单克隆抗体贝伐单抗，以及具有抗血管生成和抗增殖活性的多靶点 TKI，例如舒尼替尼。针对 HER 家族和血管生成途径的多种药物的联合治疗（例如曲妥珠单抗加贝伐珠单抗）也在临床环境中显示出活性。尽管最近取得了进展，但有关靶向药物治疗 MBC 的问题仍有待解答。未来的研究有必要确定最大化临床活性同时最小化毒性所需的最佳组合、剂量和时间表。尽管很想在所有患者中使用靶向药物，但确定最有可能受益的患者亚组必须是一个关键目标，并且对于未来成功使用这些治疗方法至关重要。本综述的目的是总结一些参与肿瘤进展的关键信号通路以及一些正在开发的 MBC 新型疗法。
This review summarizes some of the key signaling pathways involved in tumor progression and some of the novel therapies that are in development for the treatment of metastatic breast cancer patients. 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.
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影响因子：
45.3
作者：
Burstein, Harold J.;Elias, Anthony D.;Miller, Kathy D.
通讯作者：
Miller, Kathy D.
影响因子：
11.5
作者：
Arteaga, Carlos L.;O'Neill, Anne;Davidson, Nancy E.
通讯作者：
Davidson, Nancy E.
影响因子：
3.9
作者：
Barrett-Lee, PJ
通讯作者：
Barrett-Lee, PJ
影响因子：
3.1
作者：
Britten CD;Finn RS;Bosserman LD;Wong SG;Press MF;Malik M;Lum BL;Slamon DJ
通讯作者：
Slamon DJ
至少一种早期组合失败后，晚期乳腺癌中曲妥珠单抗和化学疗法的分析：一项观察性研究。
影响因子：
3.8
作者：
Bartsch R;Wenzel C;Hussian D;Pluschnig U;Sevelda U;Koestler W;Altorjai G;Locker GJ;Mader R;Zielinski CC;Steger GG
通讯作者：
Steger GG