Antibody therapy for breast cancer.
Antibody therapy for breast cancer.
复制标题
乳腺癌的抗体治疗。
作者：
A. Willems;K. Gauger;Cordula Henrichs;N. Harbeck
针对肿瘤生物学特性的靶向治疗是乳腺癌个体化治疗理念的重要组成部分。除了使用传统的化疗和/或内分泌疗法的风险适应策略外，抗体疗法已成为另一种选择。人源化单抗曲妥珠单抗(Herceptin)是第一个被批准用于晚期乳腺癌常规临床应用的新型靶向疗法。通过免疫组织化学(IHC)和/或荧光原位杂交(FISH)评估肿瘤HER2/neu蛋白过度表达和/或基因扩增的患者对姑息性曲妥珠单抗治疗或联合化疗反应良好。与内分泌治疗的新组合目前正在临床试验中进行评估。曲妥珠单抗治疗一般耐受性良好。到目前为止，只有与阿霉素联合使用才能观察到相当大的心脏毒性。因此，现在在评估进一步的化疗伙伴的试验中进行了广泛的心脏监测。在德国，寻找早期曲妥珠单抗在佐剂(如HERA，Bond006)或新佐剂(如TECHO)环境中治疗的临床试验仍在接受招募。由于只有大约25%的HER2/neu阳性乳腺癌有资格接受曲妥珠单抗治疗，因此需要针对剩余的HER2/neu阴性肿瘤进行新的靶向治疗。另一种治疗性抗体2C4(Pertuzumab，Omnitarg)目前正在进行临床评估。它与HER2/neu上的表位结合不同于曲妥珠单抗，并抑制与其他HER受体的异源二聚化。I期数据显示2C4具有良好的耐受性和临床活性。
Targeted therapies against tumor biological properties are an essential part of individualized therapy concepts in breast cancer. Next to risk-adapted strategies using conventional chemo- and/or endocrine therapies, antibody therapy has become an additional option. The humanized monoclonal antibody trastuzumab (Herceptin) is the first novel targeted therapy approved for routine clinical application in advanced breast cancer. Patients with HER2/neu protein overexpression as assessed by immunohistochemistry (IHC) and/or gene amplification as assessed by fluorescence in-situ hybridization (FISH) in their tumors respond well to palliative trastuzumab therapy, either as single agent or in combination with chemotherapy. New combinations with endocrine therapy are currently being evaluated in clinical trials. Trastuzumab therapy is generally well-tolerated. So far, considerable cardiotoxicity was seen only in combination with doxorubicin. Thus, extensive cardiomonitoring is now performed in trials assessing further chemotherapeutic partners. Clinical trials looking at early trastuzumab therapy in the adjuvant (e.g. HERA, BOND 006) or neoadjuvant (e.g. TECHNO) setting are still open for recruitment in Germany. Since only about those 25 % of breast cancers which are HER2/neu-positive are eligible for trastuzumab, novel targeted therapeutics for the remaining HER2/neu-negative tumors are needed. Another therapeutic antibody, 2C4 (Pertuzumab, Omnitarg), is currently under clinical evaluation. It binds to a different epitope on HER2/neu than trastuzumab and inhibits heterodimerization with other HER receptors. Phase I data showed that 2C4 is well tolerated and clinically active.
登录
查看更多内容
影响因子：
10.3
作者：
Paik, S;Bryant, J;Wolmark, N
通讯作者：
Wolmark, N
影响因子：
56.9
作者：
SLAMON, DJ;CLARK, GM;MCGUIRE, WL
通讯作者：
MCGUIRE, WL
影响因子：
10.3
作者：
Roche, PC;Suman, VJ;Perez, EA
通讯作者：
Perez, EA
影响因子：
45.3
作者：
Esteva, FJ;Valero, V;Hortobagyi, GN
通讯作者：
Hortobagyi, GN
影响因子：
45.3
作者：
Pegram, MD;Lipton, A;Slamon, DJ
通讯作者：
Slamon, DJ