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Evaluating the Angiogenetic Properties of Ovarian Cancer Stem-Like Cells using the Three-Dimensional Co-Culture System, NICO-1
Published on: December 5, 2020
New therapies for clear cell ovarian carcinoma
James Stewart1,2, Niamh Cunningham1, Susana Banerjee3,4
1Royal Marsden Hospital NHS Trust, London, UK.
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 function ARID1A mutations. 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 exploiting ARID1A synthetic 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.
Insights
Ovarian clear cell carcinoma (OCCC) shows poor response to chemotherapy. Novel treatments targeting angiogenesis, immune checkpoints, and ARID1A synthetic lethality are under investigation for this rare cancer.
Area of Science:
- Oncology
- Genetics
- Cancer Research
Background:
- Ovarian clear cell carcinoma (OCCC) is a rare epithelial ovarian cancer subtype.
- It is characterized by frequent ARID1A mutations and resistance to standard chemotherapy.
- Current treatment strategies are often based on trials for high-grade serous ovarian carcinoma, not tailored for OCCC.
Purpose of the Study:
- To review novel therapeutic strategies for advanced and recurrent ovarian clear cell carcinoma.
- To highlight the focus on immune checkpoint blockade, anti-angiogenesis, and ARID1A synthetic lethality.
- To identify challenges and future directions in OCCC treatment research.
Main Methods:
- Review of current clinical trials and research for ovarian clear cell carcinoma treatments.
- Analysis of molecular features, particularly ARID1A mutations.
- Assessment of emerging therapeutic strategies and their combinations.
Main Results:
- Novel treatments are being developed targeting OCCC's unique molecular profile.
- Key areas include immune checkpoint inhibitors, anti-angiogenesis therapies, and ARID1A synthetic lethal approaches.
- Combinations of these strategies are under active investigation in clinical trials.
Conclusions:
- Ovarian clear cell carcinoma requires tailored treatment strategies due to its distinct biology and chemoresistance.
- Future research must focus on identifying predictive biomarkers for novel therapies.
- International collaboration is crucial for rare cancer trials and treatment sequencing.
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