ArticleBritish journal of cancer2016
Dual CCNE1/PIK3CA targeting is synergistic in CCNE1-amplified/PIK3CA-mutated uterine serous carcinomas in vitro and in vivo.
Article in British journal of cancer, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 42 citations in OpenAlex.
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- Genomic Landscape of ctDNA and Real-World Outcomes in Advanced Endometrial Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2024Article
- Targeting CDK2 to combat drug resistance in cancer therapy.Future oncology (London, England) · 2024Review
- Integrated mutational landscape analysis of poorly differentiated high-grade neuroendocrine carcinoma of the uterine cervix.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- P129, a pyrazole ring-containing isolongifolanone-derivate: synthesis and investigation of anti-glioma action mechanism.Discover oncology · 2024Article
- Race- associated molecular differences in uterine serous carcinoma.Frontiers in oncology · 2024Article
- Critical Overview of Serous Endometrial Intraepithelial Cancer Treatment: Systematic Review of Adjuvant Options.Life (Basel, Switzerland) · 2023Review
- CDK9 inhibitors in cancer research.RSC medicinal chemistry · 2022Review
- Invasive lobular carcinoma: an understudied emergent subtype of breast cancer.Breast cancer research and treatment · 2022Review
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- Integrative molecular and clinical profiling of acral melanoma links focal amplification of 22q11.21 to metastasis.Nature communications · 2022Article
- Ipatasertib, an oral AKT inhibitor, inhibits cell proliferation and migration, and induces apoptosis in serous endometrial cancer.American journal of cancer research · 2022Article
- A Novel CDK2/9 Inhibitor CYC065 Causes Anaphase Catastrophe and Represses Proliferation, Tumorigenesis, and Metastasis in Aneuploid Cancers.Molecular cancer therapeutics · 2021Article
- Long noncoding RNA LINC01234 silencing exerts an anti-oncogenic effect in esophageal cancer cells through microRNA-193a-5p-mediated CCNE1 downregulation.Cellular oncology (Dordrecht, Netherlands) · 2020Article
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- Targeting human epidermal growth factor receptor 2 (HER2) in gynecologic malignancies.Current opinion in obstetrics & gynecology · 2020Review
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- Fadraciclib (CYC065), a novel CDK inhibitor, targets key pro-survival and oncogenic pathways in cancer.PloS one · 2020Article
- Cyclin E: a potential treatment target to reverse cancer chemoresistance by regulating the cell cycle.American journal of translational research · 2020Review
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Authors and funding
22 authors at 2 institutions in 2 countries.
Funding
Abstract
backgroundClinical options for patients harbouring advanced/recurrent uterine serous carcinoma (USC), an aggressive variant of endometrial tumour, are very limited. Next-generation sequencing (NGS) data recently demonstrated that cyclin E1 (CCNE1) gene amplification and pik3ca driver mutations are common in USC and may therefore represent ideal therapeutic targets.
methodsCyclin E1 expression was evaluated by immunohistochemistry (IHC) on 95 USCs. The efficacy of the cyclin-dependent kinase 2/9 inhibitor CYC065 was assessed on multiple primary USC cell lines with or without CCNE1 amplification. Cell-cycle analyses and knockdown experiments were performed to assess CYC065 targeting specificity. Finally, the in vitro and in vivo activity of CYC065, Taselisib (a PIK3CA inhibitor) and their combinations was tested on USC xenografts derived from CCNE1-amplified/pik3ca-mutated USCs.
resultsWe found that 89.5% of the USCs expressed CCNE1. CYC065 blocked cells in the G1 phase of the cell cycle and inhibited cell growth specifically in CCNE1-overexpressing USCs. Cyclin E1 knockdown conferred increased resistance to CYC065, whereas CYC065 treatment of xenografts derived from CCNE1-amplified USCs significantly reduced tumour growth. The combination of CYC065 and Taselisib demonstrated synergistic effect in vitro and was significantly more effective than single-agent treatment in decreasing tumour growth in xenografts of CCNE1-amplified/pik3ca-mutated USCs.
conclusionsDual CCNE1/PIK3CA blockade may represent a novel therapeutic option for USC patients harbouring recurrent CCNE1-amplified/pi3kca-mutated tumours.
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