HER2-Targeted Antibody Treatment for Ovarian Cancer Future Opportunities

There are an estimated 240,000 new cases of ovarian cancer diagnosed worldwide each year. Due to late presentation, in many parts of the world it remains the most lethal gynecological cancer. In 2004, a new model description of this disease was proposed that combined both histopathological and molecular features and which classified epithelial ovarian cancers into two broad categories designated Type I and Type II tumors. Type I tumors tend to be low grade and are exemplified by clear cell, mucinous, low-grade serous and endometrioid histologies with associated molecular alterations characterised by mutations in genes including HER2, KRAS, BRAF, CTNNB1, PTEN, PIK3CA, ARIDIA and PPPR1A. 

More recently, profiling studies have attempted to further stratify ovarian cancer into molecular subtypes, although these have largely focused on Type II, high grade serous ovarian tumors whichfrequently contain mutations in p53 and the BRCA genes. These genetic abnormalities can help define the response of cancers to specific treatments, hence the widespread use of platinum containing drugs which have useful efficacy particularly in type II disease. Platinum containing regimens are the standard of care in first line treatment of this disease. However, resistance frequently develops and there is an ongoing need for improved second line options.