The Cancer Institute of New Jersey, University of Medicine and Dentistry of New Jersey, New Brunswick, NJ 08903-2681, USA.
Am J Health Syst Pharm. 2009 Dec 1;66(23 Suppl 6):S9-S14. doi: 10.2146/ajhp090439.
To review data supporting the effectiveness of emerging treatment options for metastatic breast cancer.
Recent research has focused on several signal-transduction pathways important in the pathogenesis of breast cancer. Mammalian target of rapamycin (mTOR) is a serine-threonine protein kinase that is involved in cell growth and survival. Everolimus, an orally active inhibitor of mTOR, has demonstrated promising efficacy results and a favorable safety profile in initial studies. Epidermal growth factor receptor (EGFR), a cell-surface molecule that has been implicated in the pathogenesis of breast cancer, may also be important in the emergence of resistance to endocrine therapy. Initial clinical studies have suggested that EGFR inhibitors such as gefitinib may delay the development of resistance to endocrine therapy in patients with breast cancer when given concurrently with tamoxifen or an aromatase inhibitor. Finally, considerable recent research has examined the role of epigenetic gene silencing, in which acetylation or deacetylation of DNA modifies the expression of tumor-suppressing genes. The enzyme histone deacetylase (HDAC) suppresses gene transcription by modifying chromatin into a more compact form. HDAC inhibitors have emerged as a potential new treatment option for several cancer types, including breast cancer. The HDAC inhibitor vorinostat has recently been examined in combination with other treatments, including cytotoxic agents and bevacizumab, for the treatment of breast cancer. In one small Phase I and II study, first-line treatment with the combination of vorinostat, paclitaxel, and bevacizumab produced objective responses (partial or complete) in more than 50% of patients with recurrent or metastatic breast cancer.
Although the results of the described studies are promising, randomized controlled clinical trials are needed to better understand the efficacy and safety of emerging treatment options for patients with metastatic breast cancer.
综述新兴治疗选择对转移性乳腺癌的有效性数据。
最近的研究集中在几个对乳腺癌发病机制很重要的信号转导途径上。雷帕霉素靶蛋白（mTOR）是一种丝氨酸-苏氨酸蛋白激酶，参与细胞生长和存活。依维莫司，一种 mTOR 的口服抑制剂，在初步研究中显示出有希望的疗效结果和良好的安全性特征。表皮生长因子受体（EGFR）是一种细胞表面分子，已被牵连到乳腺癌的发病机制中，在对内分泌治疗的耐药性的出现中也可能很重要。初步的临床研究表明，当与他莫昔芬或芳香化酶抑制剂联合使用时，EGFR 抑制剂（如吉非替尼）可能会延迟乳腺癌患者对内分泌治疗的耐药性的发展。最后，最近有大量研究探讨了表观遗传基因沉默的作用，其中 DNA 的乙酰化或去乙酰化改变了肿瘤抑制基因的表达。组蛋白去乙酰化酶（HDAC）通过将染色质修饰成更紧凑的形式来抑制基因转录。HDAC 抑制剂已成为几种癌症类型（包括乳腺癌）的潜在新治疗选择。HDAC 抑制剂伏立诺他最近已与其他治疗方法（包括细胞毒性药物和贝伐单抗）联合用于治疗乳腺癌。在一项小规模的 I/II 期研究中，伏立诺他、紫杉醇和贝伐单抗联合一线治疗，使超过 50%的复发性或转移性乳腺癌患者产生客观反应（部分或完全）。
尽管描述性研究的结果很有希望，但需要进行随机对照临床试验，以更好地了解新兴治疗选择对转移性乳腺癌患者的疗效和安全性。
