ArticleMolecular cancer therapeutics2022
Targeting Therapeutic Resistance and Multinucleate Giant Cells in CCNE1-Amplified HR-Proficient Ovarian Cancer.
Article in Molecular cancer therapeutics, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 22 citations in OpenAlex.
- The Sleeping Giant: Metabolism and Autophagy in the Generation and Survival of Dormant Polyploid Giant Cancer Cells.MedComm · 2026Review
- CCNE1: A Cell Cycle Regulator That Influences Tumor Progression.Cancer medicine · 2026Review
- Tetraploids or polyploid giants: who is truly dangerous?Trends in cell biology · 2026Review
- Clinical Implications of Polyploid Giant Cancer Cells in Solid Tumors: Biology, Diagnosis, and Therapeutic Considerations.Cancers · 2026Review
- Exploring the optimal cutoff point and genomic characteristics for PARP inhibitor maintenance therapy in early recurrence of ovarian cancer.Journal of ovarian research · 2026Article
- Biomarker-Driven Treatments for Ovarian Cancer: Moving Beyond HRD?International journal of women's health · 2026Review
- Multiomic analysis of CCNE1 amplification associated molecular and immune features in gynecological cancers.Discover oncology · 2025Article
- EGFL6 is a novel HER3 ligand, inducing HER3/integrin heterodimers to induce pERK centrosomal deposition and therapeutic resistance.Neoplasia (New York, N.Y.) · 2025Article
- Unraveling Homologous Recombination Deficiency in Ovarian Cancer: A Review of Currently Available Testing Platforms.Cancers · 2025Review
- High-Throughput Empirical and Virtual Screening To Discover Novel Inhibitors of Polyploid Giant Cancer Cells in Breast Cancer.Analytical chemistry · 2025Article
- Targeting autophagy promotes the antitumor effect of radiotherapy on cervical cancer cells.Cancer biology & therapy · 2024Article
- Patterns of genomic instability in > 2000 patients with ovarian cancer across six clinical trials evaluating olaparib.Genome medicine · 2024Article
- PI3K/AKT/mTOR and PD‑1/CTLA‑4/CD28 pathways as key targets of cancer immunotherapy (Review).Oncology letters · 2024Review
- High-Throughput Empirical and Virtual Screening to Discover Novel Inhibitors of Polyploid Giant Cancer Cells in Breast Cancer.bioRxiv : the preprint server for biology · 2024Article
- Y-box binding protein 1/cyclin A1 axis specifically promotes cell cycle progression at GScientific reports · 2024Article
- Targeted and Shallow Whole-Genome Sequencing Identifies Therapeutic Opportunities in p53abn Endometrial Cancers.Clinical cancer research : an official journal of the American Association for Cancer Research · 2024Article
- Article
- Dormant cancer cells and polyploid giant cancer cells: The roots of cancer recurrence and metastasis.Clinical and translational medicine · 2024Review
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
Approximately 20% of high-grade serous ovarian cancers (HGSOC) have CCNE1 amplification. CCNE1-amplified tumors are homologous recombination (HR) proficient and resistant to standard therapies. Therapy resistance is associated with increased numbers of polyploid giant cancer cells (PGCC). We sought to identify new therapeutic approaches for patients with CCNE1-amplified tumors. Using TCGA data, we find that the mTOR, HR, and DNA checkpoint pathways are enriched in CCNE1-amplified ovarian cancers. Furthermore, Interactome Mapping Analysis linked the mTOR activity with upregulation of HR and DNA checkpoint pathways. Indeed, we find that mTOR inhibitors (mTORi) downregulate HR/checkpoint genes in CCNE1-amplified tumors. As CCNE1-amplified tumors are dependent on the HR pathway for viability, mTORi proved selectively effective in CCNE1-amplified tumors. Similarly, via downregulation of HR genes, mTORi increased CCNE1-amplifed HGSOC response to PARPi. In contrast, overexpression of HR/checkpoint proteins (RAD51 or ATR), induced resistance to mTORi. In vivo, mTORi alone potently reduced CCNE1-amplified tumor growth and the combination of mTORi and PARPi increased response and tumor eradication. Tumors treated with mTORi demonstrated a significant reduction in ALDH+ PGCCs. Finally, as a proof of principle, we identified three patients with CCNE1 amplified tumors who were treated with an mTORi. All three obtained clinical benefits from the therapy. Our studies and clinical experience indicate mTORi are a potential therapeutic approach for patients with CCNE1-amplified tumors.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.