Issues regarding improving the impact of antiangiogenic drugs for the treatment of breast cancer.
Issues regarding improving the impact of antiangiogenic drugs for the treatment of breast cancer.
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DOI：
10.1016/s0960-9776(09)70271-1
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发表时间：
2009-10
期刊：
影响因子：
--
通讯作者：
Kerbel RS
中科院分区：
文献类型：
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作者：
Kerbel RS
最近癌症治疗的主要临床进展之一是使用抗血管生成药物，如贝伐单抗、索拉非尼和舒尼替尼。贝伐单抗是抗血管内皮生长因子的单抗，已被批准与紫杉烷联合用于转移性乳腺癌(MBC)的一线治疗。然而，临床益处不大；尽管应答率翻了一番，无进展生存时间显著延长，但总体生存没有增加。这篇综述总结了解释这一差异结果的一些可能性。这些包括由于血管生成原生长因子的冗余而导致的获得性耐药性的快速发展，抗血管生成药物治疗停止后肿瘤的加速生长，以及由肿瘤缺氧增加等机制驱动的肿瘤细胞恶性侵袭性的增加。讨论了一些可能的策略来提高抗血管生成药物治疗的益处，如延长治疗超过肿瘤进展，结合其他治疗方式，如长期(‘维持’)小剂量节律化疗或额外的靶向/生物药物，如曲妥珠单抗。
One of the major recent clinical advances in cancer treatment is the use of antiangiogenic drugs such as bevacizumab, sorafenib, and sunitinib. Bevacizumab, the monoclonal anti-VEGF antibody, has been approved for the first line treatment of metastatic breast cancer (MBC) when combined with taxane. However, the clinical benefits are modest; despite a doubling of response rates and significant prolongation of progression free survival times, no increase in overall survival is attained. This review summarizes some of the possibilities to account for this discrepant result. These include rapid development of acquired drug resistance due to the redundancy of proangiogenic growth factors, acceleration of tumor growth after antiangiogenic drug treatments are stopped, and increases in tumor cell malignant aggressiveness driven by mechanisms such as increased tumor hypoxia. Some possible strategies to improve the benefits of antiangiogenic drug therapy are discussed such as prolonging the treatment beyond tumor progression, combination with other therapeutic modalities, e.g. long term (‘maintenance’) low-dose metronomic chemotherapy or additional targeted/biologic drugs, e.g. trastuzumab.