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Role of trastuzumab in the management of HER2-positive metastatic breast cancer

机译:曲妥珠单抗在HER2阳性转移性乳腺癌治疗中的作用

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摘要

Breast cancer is a major health issue in developed countries. Overexpression of HER2, a member of epidermal growth factor receptor family, occurs in 20%–30% of breast cancers. HER2 drives the cancer cells to develop a more aggressive phenotype, to metastasize to viscera and central nervous system, and to be less sensitive to chemotherapeutic agents. Trastuzumab (Herceptin®) is a monoclonal antibody directed against the extracellular domain of HER2. As single agent or with chemotherapy, trastuzumab improves survival of HER2-positive breast cancers. In the past years, trastuzumab has completely revolutionized the scenario of the treatment of HER2-positive breast cancer, representing one of the most remarkable examples of targeted therapy in oncology. However, issues such as the best chemotherapeutic companion to associate with trastuzumab, cardiac toxicities, and clinical resistance still require tremendous efforts by researchers. Here, we review pharmacology, efficacy studies, and toxicities of trastuzumab in metastatic breast cancer. Moreover, we provide some insights on resistance to therapy. Finally, we briefly discuss trastuzumab’s place in the clinical setting.
机译:乳腺癌是发达国家的主要健康问题。 HER2(表皮生长因子受体家族的成员)的过表达发生在20%–30%的乳腺癌中。 HER2驱动癌细胞发展更具侵略性的表型,转移至内脏和中枢神经系统,并且对化疗药物的敏感性降低。曲妥珠单抗(Herceptin®)是针对HER2胞外域的单克隆抗体。作为单一药物或联合化疗,曲妥珠单抗可改善HER2阳性乳腺癌的生存率。在过去的几年中,曲妥珠单抗彻底改变了治疗HER2阳性乳腺癌的方法,代表了肿瘤靶向治疗的最杰出实例之一。然而,诸如与曲妥珠单抗相关的最佳化学治疗伴侣,心脏毒性和临床耐药性等问题仍需要研究人员付出巨大的努力。在这里,我们回顾了曲妥珠单抗在转移性乳腺癌中的药理,功效研究和毒性。此外,我们提供了有关抗药性的一些见解。最后,我们简要讨论曲妥珠单抗在临床中的地位。

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