HER2 Oncogene as Molecular Target in Uterine Serous Carcinoma and Uterine Carcinosarcoma

SIMPLE SUMMARY: There are several types of uterine cancer. Two of the more rare types are uterine serous carcinoma and carcinosarcoma, which are both very aggressive forms. These rare, aggressive types often have mutations that allow them to be treated with specific therapies that are targeted. One such mutation causes an increase in proteins named HER2 on the tumor cell surfaces. This article summarizes the evidence behind all of the different HER2-targeting therapies for uterine serous carcinoma and uterine carcinosarcoma. ABSTRACT: Uterine serous carcinoma (USC) and uterine carcinosarcoma (UCS) are two rare histologic variants of uterine carcinoma, with distinct molecular profiles and aggressive metastatic potential. As the effectivity of traditional platinum-based chemotherapy for USC and UCS is low, and there are high rates of resistance and recurrence, the development of novel targeted therapeutics is needed. Human epidermal growth factor receptor 2 (HER2) has proven to be an oncogene of increasing interest in these cancers, as HER2 protein overexpression and/or c-ERBB2 gene amplification ranges from ~30 to 35% in USC, and between ~15 and 20% in UCS. This review summarizes the existing clinical and preclinical evidence, as well as ongoing clinical trials of HER2-targeting therapeutics, and identifies potential areas of further development and inquiry.