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Potential targets for ovarian clear cell carcinoma: a review of updates and future perspectives
Shinya Matsuzaki1, Kiyoshi Yoshino1, Yutaka Ueda1
1Department of Obstetrics and Gynecology, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka 565-0871 Japan.
Abstract:
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.
Insights
Clear cell ovarian cancer shows resistance to platinum drugs, necessitating new targeted therapies. This review explores platinum resistance mechanisms and novel treatment strategies for improved patient outcomes.
Area of Science:
- Gynecologic Oncology
- Cancer Therapeutics
- Molecular Biology
Background:
- Ovarian cancer prognosis has improved due to advances in treatments.
- Platinum drugs are crucial for ovarian cancer therapy.
- Clear cell carcinoma (CCC) subtypes exhibit resistance to platinum drugs, leading to poor prognoses.
Purpose of the Study:
- To review current medical treatments for clear cell ovarian cancer.
- To discuss future prospects for clear cell ovarian cancer therapy.
- To focus on platinum resistance mechanisms and targeted therapies for CCC.
Main Methods:
- Review of literature on clear cell ovarian cancer treatments.
- Analysis of platinum resistance mechanisms, including annexin A4, VEGF, PI3K/AKT/mTOR, ARID1A, HNF-1β, and ZNF217.
- Examination of targeted molecular therapeutics for epithelial ovarian cancer and their role in CCC.
Main Results:
- Clear cell ovarian cancer, particularly prevalent in Japan, shows poor response to standard chemotherapy.
- Mechanisms of platinum resistance involve factors like annexin A4, VEGF, PI3K/AKT/mTOR pathway, ARID1A, HNF-1β, and ZNF217.
- Targeted therapies including anti-angiogenesis, growth factor inhibitors, and signaling pathway modulators show potential.
Conclusions:
- Novel targeted therapies are essential for treating platinum-resistant clear cell ovarian cancer.
- Understanding resistance mechanisms is key to developing effective treatments.
- This review provides insights into potential therapeutic strategies for ovarian clear cell carcinoma.
