New therapies for clear cell ovarian carcinoma

Abstract

Ovarian clear cell carcinoma is a rare subtype of epithelial ovarian cancer with unique clinicopathological features. The most common genetic aberration observed is loss of functionARID1Amutations. Advanced and recurrent ovarian clear cell carcinoma is characterized by resistance to standard-of-care cytotoxic chemotherapy and a poor prognosis. Despite the distinct molecular features of ovarian clear cell carcinoma, current treatments for this subtype of epithelial ovarian cancer are based on clinical trials which predominantly recruited patients with high grade serous ovarian carcinoma. These factors have encouraged researchers to develop novel treatment strategies specifically for ovarian clear cell carcinoma which are currently being tested in the context of clinical trials. These new treatment strategies currently focus on three key areas: immune checkpoint blockade, targeting angiogenesis, and exploitingARID1Asynthetic lethal interactions. Rational combinations of these strategies are being assessed in clinical trials. Despite the progress made in identifying new treatments for ovarian clear cell carcinoma, predictive biomarkers to better define those patients likely to respond to new treatments remain to be elucidated. Additional future challenges which may be addressed through international collaboration include the need for randomized trials in a rare disease and establishing the relative sequencing of these novel treatments.

Application of interpretable machine learning algorithms to predict distant metastasis in ovarian clear cell carcinoma

“…OCCC accounts for approximately 5%–20% of all ovarian cancer cases, with notable variations in incidence across different racial and geographical groups. Its prevalence is approximately 3.1% in the black population, 4.8% in the white population, and 11.1% among individuals of Asian descent 7,8 . Notably, the Asian region, particularly Japan, exhibits the highest incidence of OCCC, with rates reaching up to 25% 9 …”

“…Its prevalence is approximately 3.1% in the black population, 4.8% in the white population, and 11.1% among individuals of Asian descent. 7,8 Notably, the Asian region, particularly Japan, exhibits the highest incidence of OCCC, with rates reaching up to 25%. 9 While OCCC is relatively straightforward to diagnose at an early stage, its inherent insensitivity to platinumbased chemotherapy regimens contributes to a heightened risk of infiltration, metastasis, and relapse after treatment, resulting in a markedly unfavorable prognosis.…”

Pembrolizumab and lenvatinib in recurrent ovarian clear cell carcinoma resistant to chemotherapy

“…Ovarian clear cell carcinoma (CCC) is a rare histologic subtype of epithelial ovarian carcinoma, and accounts for 5–25% of all epithelial ovarian carcinoma cases, depending on geographic location ( Banerjee and Kaye, 2013 ). Despite having clinical, histopathological, and genetic characteristics that differ from high grade serous ovarian carcinoma (HGSC), the most common subtype of ovarian cancer, the treatment pathways have remained the same, mostly due to a paucity of clinical data specific for ovarian CCC ( Stewart et al, 2023 ). Standard treatment involves aggressive cytoreductive surgery followed by systemic platinum-based chemotherapy.…”

“…As loss of ARID1A function has been associated with increased microsatellite instability and tumor mutational burden, targeting immune checkpoint blockade represents a promising potential treatment strategy for ovarian CCC ( Shen et al, 2018 ). Furthermore, there is early clinical evidence that ovarian CCC may respond more favorably to anti-PD-L1 agents than HGSC ( Stewart et al, 2023 , Matulonis et al, 2019 ). As it is thought that ovarian CCC progression is due in part to VEGF-mediated angiogenesis, targeting angiogenesis is another potential treatment pathway ( Stewart et al, 2023 ).…”

Novel therapies leading to a new landscape in gynecologic tumors

“…Furthermore, research and innovation in less common tumors, such as gestational trophoblastic tumors, low grade serous, and clear cell ovarian carcinoma have also revealed new therapeutic opportunities, optimizing efficacy, and reducing potential toxicity. [6][7][8] This special issue showcases review articles by world leaders in gynecologic oncology discussing the biology of gynecologic tumors, rationale and development of new therapeutic approaches, clinical trial design and interpretation, and novel drug related adverse event management.…”