Sato Ko, Rajendra Eeson, Ohta Tomohiko
Division of Breast and Endocrine Surgery, St Marianna University School of Medicine, Kawasaki, 216-8511, Japan.
BMC Biochem. 2008 Oct 21;9 Suppl 1(Suppl 1):S2. doi: 10.1186/1471-2091-9-S1-S2.
During the past decade, progress in endocrine therapy and the use of trastuzumab has significantly contributed to the decline in breast cancer mortality for hormone receptor-positive and ERBB2 (HER2)-positive cases, respectively. As a result of these advances, a breast cancer cluster with poor prognosis that is negative for the estrogen receptor (ESR1), the progesterone receptor (PRGR) and ERBB2 (triple negative) has come to the forefront of medical therapeutic attention. DNA microarray analyses have revealed that this cluster is phenotypically most like the basal-like breast cancer that is caused by deficiencies in the BRCA1 pathways. To gain further improvements in breast cancer survival, new types of drugs might be required, and small molecules targeting the ubiquitin proteasome system have moved into the spotlight. The success of bortezomib in the treatment of multiple myeloma has sent encouraging signals that proteasome inhibitors could be used to treat other types of cancers. In addition, ubiquitin E3s involved in ESR1, ERBB2 or BRCA1 pathways could be ideal targets for therapeutic intervention. This review summarizes the ubiquitin proteasome pathways related to these proteins and discusses the possibility of new drugs for the treatment of breast cancers. PUBLICATION HISTORY : Republished from Current BioData's Targeted Proteins database (TPdb; http://www.targetedproteinsdb.com).
在过去十年中，内分泌治疗的进展以及曲妥珠单抗的使用，分别显著降低了激素受体阳性和ERBB2（HER2）阳性乳腺癌患者的死亡率。由于这些进展，雌激素受体（ESR1）、孕激素受体（PRGR）和ERBB2均为阴性（三阴性）的预后不良乳腺癌群体已成为医学治疗关注的焦点。DNA微阵列分析表明，该群体在表型上最类似于由BRCA1通路缺陷引起的基底样乳腺癌。为了进一步提高乳腺癌患者的生存率，可能需要新型药物，而靶向泛素蛋白酶体系统的小分子药物已成为关注焦点。硼替佐米治疗多发性骨髓瘤的成功发出了令人鼓舞的信号，即蛋白酶体抑制剂可用于治疗其他类型的癌症。此外，参与ESR1、ERBB2或BRCA1通路的泛素E3可能是治疗干预的理想靶点。本综述总结了与这些蛋白相关的泛素蛋白酶体通路，并讨论了用于治疗乳腺癌的新药的可能性。发表历史：转载自Current BioData的靶向蛋白数据库（TPdb；http://www.targetedproteinsdb.com）。
