The role of HER2 in cancer therapy and targeted drug delivery.
The role of HER2 in cancer therapy and targeted drug delivery.
复制标题
DOI：
10.1016/j.jconrel.2010.04.009
复制
发表时间：
2010-09-15
期刊：
影响因子：
--
通讯作者：
Cheng K
中科院分区：
文献类型：
--
作者：
Tai W;Mahato R;Cheng K
HER2在相当大比例的乳腺癌、卵巢癌和胃癌中高度表达。自从发现其在肿瘤发生中的作用以来，HER2在过去二十年中在癌症研究中受到极大关注。用于治疗乳腺癌的人源化单克隆抗HER2抗体（曲妥珠单抗）的成功开发进一步刺激了科学家开发用于癌症治疗的各种HER2特异性抗体、二聚化抑制剂和激酶抑制剂。另一方面，HER2的高表达及其胞外结构域的可接近性使HER2成为抗肿瘤药物以及成像剂靶向递送的理想靶标。虽然没有针对HER2的天然配体，但是已经开发了各种靶向HER2的人工配体并将其应用于各种靶向药物递送系统。本文就HER2在肿瘤治疗和靶向给药中的作用作一综述。将简要描述HER2的结构和信号通路。HER2在肿瘤发生中的作用及其与其他肿瘤标志物的关系将被讨论。针对HER2靶向肿瘤治疗，本文将总结包括阻断受体二聚化、抑制酪氨酸激酶活性和阻断下游信号通路在内的多种策略。对于向HER2阳性肿瘤细胞的靶向药物递送，将详细描述各种靶向配体及其递送系统。
HER2 is highly expressed in a significant proportion of breast cancer, ovarian cancer, and gastric cancer. Since the discovery of its role in tumorigenesis, HER2 has received great attention in cancer research during the past two decades. Successful development of the humanized monoclonal anti-HER2 antibody (Trastuzumab) for the treatment of breast cancer further spurred scientists to develop various HER2 specific antibodies, dimerization inhibitors and kinase inhibitors for cancer therapy. On the other hand, the high expression of HER2 and the accessibility of its extracellular domain make HER2 an ideal target for the targeted delivery of anti-tumor drugs as well as imaging agents. Although there is no natural ligand for HER2, various artificial ligands targeting HER2 have been developed and applied in various targeted drug delivery systems. The emphasis of this review is to elucidate the roles of HER2 in cancer therapy and targeted drug delivery. The structure and signal pathway of HER2 will be briefly described. The role of HER2 in tumorigenesis and its relationship with other tumor markers will be discussed. For the HER2 targeted cancer therapy, numerous strategies including the blockage of receptor dimerization, inhibition of the tyrosine kinase activity, and interruption of the downstream signal pathway will be summarized. For the targeted drug delivery to HER2 positive tumor cells, various targeting ligands and their delivery systems will be described in details.
登录
查看更多内容
影响因子：
5.7
作者：
Afshar S;Asai T;Morrison SL
通讯作者：
Morrison SL
影响因子：
50.3
作者：
Agus, DB;Akita, RW;Sliwkowski, MX
通讯作者：
Sliwkowski, MX
影响因子：
82.9
作者：
Craft, N;Shostak, Y;Sawyers, CL
通讯作者：
Sawyers, CL
影响因子：
5.7
作者：
Cho, HM;Rosenblatt, JD;Shin, SU
通讯作者：
Shin, SU
影响因子：
45.3
作者：
Bookman, MA;Darcy, KM;Horowitz, IR
通讯作者：
Horowitz, IR