Suzuki Yasuhiro, Saito Yuki, Okamura Takuho, Tokuda Yutaka
Dept. of Breast and Endocrine Surgery, Tokai University School of Medicine.
Gan To Kagaku Ryoho. 2011 Jun;38(6):892-5.
There are four members of the ErbB family: the epidermal growth factor(EGF)receptor(also called HER1 or EGFR), HER2, HER3 and HER4. Dimerization is the process whereby two HER receptor molecules associate to form a noncovalent complex. HER dimers are the active receptor forms required for transmission of external stimuli to the interior of the cell. HER dimerization occurs upon ligand binding and both HER homodimers and heterodimers can be formed in the process. However, HER2 appears to be the preferred dimerization partner of the other HER family members. Fifteen∼20% of all breast cancers are HER2 positive and have a poor prognosis. Trastuzumab is an excellent, rationally-designed targeted cancer treatment. It is a recombinant, humanized, anti-HER2 monoclonal antibody that specifically binds to the extracellular area of HER2. However, the overall trastuzumab response rate is low, and the causes of trastuzumab resistance are poorly understood. Thus, there is a need for alternative anti-HER2 strategies for trastuzumab-resistant disease. Lapatinib is an orally administered small-molecule, reversible inhibitor of both EGFR and HER2 tyrosine kinase, and its activities include subsequent inhibition of its down- stream MAPK-ERK1/2, and the AKT signaling pathway. Lapatinib is more active when used in combination with capecitabine. For women with trastuzumab pre-treated HER2-positive breast cancer, Here, I will review the basics of EGFR and HER, and the treatment strategy for HER2-positive breast cancer with lapatinib.
ErbB家族有四个成员：表皮生长因子（EGF）受体（也称为HER1或EGFR）、HER2、HER3和HER4。二聚化是两个HER受体分子缔合形成非共价复合物的过程。HER二聚体是将外部刺激传递到细胞内部所需的活性受体形式。HER二聚化在配体结合时发生，在此过程中可以形成HER同二聚体和异二聚体。然而，HER2似乎是其他HER家族成员首选的二聚化伙伴。所有乳腺癌中有15%至20%为HER2阳性，预后较差。曲妥珠单抗是一种出色的、合理设计的靶向癌症治疗药物。它是一种重组人源化抗HER2单克隆抗体，特异性结合HER2的细胞外区域。然而，曲妥珠单抗的总体反应率较低，且对曲妥珠单抗耐药的原因了解甚少。因此，对于曲妥珠单抗耐药的疾病，需要替代的抗HER2策略。拉帕替尼是一种口服的小分子、可逆的EGFR和HER2酪氨酸激酶抑制剂，其活性包括随后抑制其下游的MAPK-ERK1/2和AKT信号通路。拉帕替尼与卡培他滨联合使用时活性更高。对于接受过曲妥珠单抗预处理的HER2阳性乳腺癌女性，在此，我将回顾EGFR和HER的基础知识，以及拉帕替尼治疗HER2阳性乳腺癌的策略。
