赫賽汀可能用于治療HER2陰性乳腺癌

2013年2月28日 | Filed under: 藥物化學,文獻綜合 | Posted by: 編輯 D

作者：朱貴東

眾所周知，大約百分之二十的乳腺癌呈人類表皮細胞受體2（HER2）陽性，大量臨床結(jié)果證明，使用羅氏制藥的單克隆抗體赫賽汀（Herceptin，通用名：Trastuzumab）治療，尤其在手術(shù)摘除腫瘤后和其它抗腫瘤藥物聯(lián)合配用，能顯著延長患者的生存期。

但是，長久以來人們一直認為赫賽汀只對HER2陽性的乳腺癌患者有效，道理很簡單，赫賽汀是靶向HER2的單克隆抗體。現(xiàn)在這個概念受到挑戰(zhàn)。美國密執(zhí)安大學癌癥綜合研究中心的研究人員經(jīng)過整理、分析過去臨床實驗結(jié)果發(fā)現(xiàn)，一部分HER2陰性的乳腺癌患者曾被錯誤地診斷為HER2陽性，因而得到赫賽汀治療，而且療效和HER2陽性的乳腺癌患者類似。體外以及動物實驗表明，HER2對傳統(tǒng)歸類為HER2陰性的乳腺癌也起著關(guān)鍵性作用，赫賽汀能抑制這類腫瘤的生長和擴散。除此之外，密執(zhí)安大學的科學家還給出解釋這個令人驚訝結(jié)果的分子機理。如果這個結(jié)果得以在臨床實驗中證實，將改革現(xiàn)行乳腺癌的治療模式。研究還表明，對于HER2陰性的乳腺癌，骨轉(zhuǎn)移的HER2表達要更高。這些研究結(jié)果發(fā)表在今天上線的《癌癥研究》（Cancer Research）雜志上。

【原文摘要】

HER2 Drives Luminal Breast Cancer Stem Cells in the Absence of HER2 Amplification: Implications for Efficacy of Adjuvant Trastuzumab

Although current breast cancer treatment guidelines limit the use of HER2-blocking agents to tumors with HER2 gene amplification, recent retrospective analyses suggest that a wider group of patients may benefit from this therapy. Using breast cancer cell lines, mouse xenograft models and matched human primary and metastatic tissues, we show that HER2 is selectively expressed in and regulates self-renewal of the cancer stem cell (CSC) population in estrogen receptor-positive (ERt), HER2_ luminal breast cancers. Although trastuzumab had no effects on the growth of established luminal breast cancer mouse xenografts, administration after tumor inoculation blocked subsequent tumor growth. HER2 expression is increased in luminal tumors grown in mouse bone xenografts, as well as in bone metastases from patients with breast cancer as compared with matched primary tumors. Furthermore, this increase in HER2 protein expression was not due to gene amplification but rather was mediated by receptor activator of NF-kB (RANK)-ligand in the bone microenvironment. These studies suggest that the clinical efficacy of adjuvant trastuzumab may relate to the ability of this agent to target the CSC population in a process that does not require HER2 gene amplification. Furthermore, these studies support a CSC model in which maximal clinical benefit is achieved when CSC targeting agents are administered in the adjuvant setting. Cancer Res; 73(5); 1–11. _2013 AACR.