Marcinkowska Monika, Stańczyk Maciej, Klajnert-Maculewicz Barbara
Katedra Biofizyki Ogólnej, Wydział Biologii i Ochrony Środowiska, Uniwersytet Łódzki.
Oddział Chirurgii Onkologicznej, Regionalny Ośrodek Onkologiczny, Wojewódzki Szpital Specjalistyczny im. Kopernika w Łodzi.
Postepy Hig Med Dosw (Online). 2015 Jan 2;69:1313-24. doi: 10.5604/17322693.1184555.
Breast cancer is the most frequently occurring cancer in women. It has been confirmed that approximately 30% of patients have overexpression of human epidermal growth factor 2 (HER2) on the surface of tumor cells. Trastuzumab - a recombinant, humanized monoclonal antibody - is directed against this receptor. Its use in traditional chemotherapy (with anthracyclines or taxanes) causes an increase of therapy efficiency. However, the systemic toxicity of the anticancer drugs is still a serious problem. Therefore, new solutions are sought, especially in the field of selective drug transport to tumor cells. Dendrimers are composed of a core and branches. They are the bestknown group of nanoparticles. A lot of publications have shown that they can be used as carriers of various types of molecules, including anticancer drugs. The branched structure provides effective protection against premature release of the drug into the circulatory system. It gives a chance to reduce the dose while maintaining a therapeutic effect, and to reduce the toxicity of the drug for normal cells. Furthermore, the surface of dendrimers can be modified by a monoclonal antibody to achieve a targeted therapy. For that reason synthesis of conjugates of trastuzumab, dendrimers, and anticancer drugs is so crucial. This paper presents an overview of publications about the use of trastuzumab in in vitro, in vivo and clinical studies, as well as the latest developments of biology and chemistry, whose goal is to create the perfect, targeted carrier.
乳腺癌是女性中最常见的癌症。已证实约30%的患者肿瘤细胞表面存在人表皮生长因子2(HER2)过表达。曲妥珠单抗——一种重组人源化单克隆抗体——针对该受体。它与传统化疗(联合蒽环类药物或紫杉烷类药物)联用可提高治疗效果。然而,抗癌药物的全身毒性仍是一个严重问题。因此,人们在寻求新的解决方案,尤其是在选择性药物转运至肿瘤细胞领域。树枝状大分子由核心和分支组成。它们是最知名的纳米颗粒类型。许多出版物表明,它们可用作包括抗癌药物在内的各种类型分子的载体。其分支结构可有效防止药物过早释放到循环系统中。这为在维持治疗效果的同时降低剂量以及减少药物对正常细胞的毒性提供了机会。此外,树枝状大分子的表面可通过单克隆抗体进行修饰以实现靶向治疗。因此,曲妥珠单抗、树枝状大分子和抗癌药物缀合物的合成至关重要。本文概述了有关曲妥珠单抗在体外、体内和临床研究中的应用的出版物,以及生物学和化学领域的最新进展,其目标是创建完美的靶向载体。