Advances in surgical and medical treatments for
ovarian cancer have improved prognoses.
Platinum drugs in particular are pivotal for the medical treatment of
ovarian cancer. However, previous studies have revealed that some histological subtypes, such as clear cell
carcinoma, are resistant to medical treatment, including that with
platinum drugs. Consequently, the clinical prognosis of advanced clear cell
carcinoma is remarkably inferior, primarily because of its chemoresistant behavior. The prevalence of clear cell
carcinoma is approximately 5 % in the West, but in Japan, its prevalence is particularly high, at approximately 25 %. Current medical treatments for advanced clear cell
carcinoma are difficult to administer, and they have poor efficacy, warranting the development of novel target-based
therapies. In this review, we describe medical treatments for clear cell
carcinoma and discuss future prospects for
therapy. In particular, we focus on the mechanism of
platinum resistance in clear cell
carcinoma, including the role of
annexin A4, one of the most investigated factors of
platinum resistance, as well as the mutant genes and overexpressed
proteins such as
VEGF, PI3K/AKT/mTOR signaling pathway, ARID1A, hepatocyte nuclear factor-1β, ZNF217. We also review targeted molecular
therapeutics for
epithelial ovarian cancer and discuss their role in clear cell
carcinoma treatment. We review the drugs targeting angiogenesis (
bevacizumab,
sorafenib, and
pazopanib),
growth factors (
gefitinib,
erlotinib,
lapatinib,
trastuzumab, and
AMG479), and signaling pathways (
temsirolimus,
dasatinib, and
imatinib), and other drugs (
oregovomab,
volociximab, and
iniparib). This current review summarizes and discusses the clinical significance of these factors in ovarian clear cell
carcinoma as well as their potential mechanisms of action. It may provide new integrative understanding for future studies on their exact role in ovarian clear cell
carcinoma.