Treating high-grade serous ovarian cancer driven by CCNE1 overexpression
Project 2: Targeting CCNE1 overexpression in high grade serous ovarian cancer
This project aims to use WEE1 inhibitors such as ZN-c3, along with molecular tumor testing, to help people with high-grade serous ovarian cancer whose tumors overexpress CCNE1 or have developed resistance to PARP inhibitors.
Quick facts
| Grant type | NIH-funded research |
|---|---|
| Study type | NIH-funded research |
| Funding institution | Johns Hopkins University NIH-funded |
| Lab location | 1 site (Baltimore, United States) |
| Project ID | NIH-11194320 on NIH RePORTER |
What this research studies
If you have high-grade serous ovarian cancer with CCNE1 overexpression, researchers will test your tumor sample for CCNE1 changes and may offer treatment with WEE1 inhibitors like ZN-c3 that push cancer cells into fatal DNA replication errors. The team previously showed that combining PARP and ATR inhibitors restored responses in BRCA-mutant tumors and found CCNE1 amplification can emerge with PARP inhibitor resistance. They plan to use detailed molecular profiling of patient tumors to validate CCNE1 amplification as a biomarker to select patients most likely to benefit and to find additional predictive markers. The work includes clinical trials, genomic testing of tumor samples, and treatment of eligible patients at Johns Hopkins and partner centers.
Who could benefit from this research
Good fit: Ideal candidates are people with high-grade serous ovarian cancer whose tumors show CCNE1 amplification or overexpression, especially those who have progressed after PARP inhibitor therapy or have BRCA-related disease.
Not a fit: Patients whose tumors do not overexpress or amplify CCNE1, or who cannot tolerate WEE1 inhibitor therapy, are less likely to benefit from this approach.
Why it matters
Potential benefit: If successful, this work could give a new targeted treatment option and better outcomes for patients whose high-grade serous ovarian tumors overexpress CCNE1 or who have become resistant to PARP inhibitors.
How similar studies have performed: Prior work showed a 50% response rate for combined PARP and ATR inhibition in BRCA-mutant HGSC and clinical activity for WEE1 inhibitors in CCNE1-overexpressing tumors, with ZN-c3 showing reduced hematologic toxicity in Phase I testing.
Where this research is happening
Baltimore, United States
- Johns Hopkins University — Baltimore, United States (Active)
Researchers
- Principal investigator: Simpkins, Fiona — Johns Hopkins University
- Study coordinator: Simpkins, Fiona
About this research
- This is an active NIH-funded research project — typically early-stage science, not a clinical trial accepting patient enrollment.
- Some NIH-funded labs run parallel clinical studies or seek volunteers for related work. To check, contact the principal investigator or institution listed above.
- For full project details, budget, and progress reports, visit the official NIH RePORTER page below.