Related Experiment Video
Updated: Mar 24, 2026
Testing Targeted Therapies in Cancer using Structural DNA Alteration Analysis and Patient-Derived Xenografts
Published on: July 25, 2020
Molecular Profiling of Clear Cell Ovarian Cancers: Identifying Potential Treatment Targets for Clinical Trials
Michael L Friedlander1, Kenneth Russell, Sherri Millis
1Prince of Wales Hospital, Prince of Wales Clinical School UNSW, Sydney, New South Wales, Australia.
Background:
Advanced stage/recurrent clear cell ovarian cancers (CCOCs) are characterized by a low response to chemotherapy and a poor prognosis. There is growing interest in investigating novel/molecular targeted therapies in patients with CCOC in histotype-specific trials. However, CCOCs are not a uniform entity and comprise a number of molecular subtypes and it is unlikely that a single approach to treatment will be appropriate for all patients. The aim of this study was to analyze the results of a multiplatform profiling panel in CCOCs to identify potential therapeutic targets.
Patients And Methods:
Tumor profiling was performed on 521 CCOCs. They were grouped into pure (n = 422) and mixed (n = 99) CCOC for analysis. Testing included a combination of DNA sequencing (including next-generation sequencing) using a 46-gene panel, immunohistochemistry, fluorescent or chromogenic in situ hybridization, and RNA fragment analysis.
Results:
The most common findings were in the PIK3CA/Akt/mTOR pathway, with 61% of all CCOCs showing a molecular alteration in one of these pathway components. Next-generation sequencing revealed PIK3CA mutations in 50% of pure CCOCs. Significant differences were observed between pure and mixed CCOCs with respect to hormone receptor expression (9% vs 34.7% for ER, 13.45 vs 26.4% for PR), cMET (24.1% vs 11.6%), PD-1 tumor infiltrating lymphocytes (48.1% vs 100%), expression of PD-L1 (7.4% vs 25%), and TOPO1 (41% vs 27.1%) on immunohistochemistry, whereas next-generation sequencing revealed significant differences in mutation frequency in PIK3CA (50% vs 18.5%), TP53 (18.1% vs 57.7%), KRAS (12.4% vs 3.7%), and cMET (1.9% vs 11.1%).
Conclusions:
This large study confirms that the PIK3CA/Akt/mTOR pathway is commonly altered in CCOCs, and highlights the significant differences between pure and mixed CCOCs. Clear cell ovarian cancers are molecularly heterogeneous and there are a number of potential therapeutic targets which could be tested in clinical trials.
Insights
Advanced stage clear cell ovarian cancers (CCOCs) show common alterations in the PIK3CA/Akt/mTOR pathway. This study identified significant molecular differences between pure and mixed CCOCs, revealing diverse therapeutic targets for clinical trials.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Advanced stage/recurrent clear cell ovarian cancers (CCOCs) have poor prognosis and low chemotherapy response.
- Histotype-specific trials for novel molecular targeted therapies are of growing interest.
- CCOCs are molecularly heterogeneous, necessitating tailored treatment approaches.
Purpose of the Study:
- To analyze multiplatform profiling data in CCOCs.
- To identify potential therapeutic targets based on molecular subtypes.
- To understand the molecular differences between pure and mixed CCOCs.
Main Methods:
- Multiplatform tumor profiling of 521 CCOCs (pure n=422, mixed n=99).
- Utilized DNA sequencing (46-gene panel, next-generation sequencing), immunohistochemistry, in situ hybridization, and RNA fragment analysis.
- Comparative analysis of molecular alterations between pure and mixed CCOC subtypes.
Main Results:
- The PIK3CA/Akt/mTOR pathway was altered in 61% of CCOCs.
- PIK3CA mutations found in 50% of pure CCOCs.
- Significant differences observed in hormone receptor expression, cMET, PD-1, PD-L1, TOPO1, PIK3CA, TP53, KRAS, and cMET mutations between pure and mixed CCOCs.
Conclusions:
- The PIK3CA/Akt/mTOR pathway is a common target in CCOCs.
- Pure and mixed CCOCs exhibit distinct molecular profiles.
- Molecular heterogeneity in CCOCs presents multiple therapeutic targets for clinical investigation.
More Related Videos
11:51Preparation of Mitochondria from Ovarian Cancer Tissues and Control Ovarian Tissues for Quantitative Proteomics Analysis
Published on: November 18, 2019
09:08Integration of Bioinformatics Approaches and Experimental Validations to Understand the Role of Notch Signaling in Ovarian Cancer
Published on: January 12, 2020
