ArticleNeoplasia (New York, N.Y.)2019
Blocking Mitotic Exit of Ovarian Cancer Cells by Pharmaceutical Inhibition of the Anaphase-Promoting Complex Reduces Chromosomal Instability.
Article in Neoplasia (New York, N.Y.), 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 40 citations in OpenAlex.
- Epigenetic Regulation of Chromosomal Instability by EZH2 Methyltransferase.Cancer discovery · 2026Article
- The Crosstalk Between CRL5 and APC/C E3 Ligases Regulates Metastasis and Chemosensitivity of Cancer Cells.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Probabilistic modeling of cell cycle dynamics in response to cell cycle targeting chemotherapy drugs to guide treatment strategies.PLoS computational biology · 2025Article
- Signaling networks and MiRNA crosstalk in ovarian cancer chemoresistance.Journal of ovarian research · 2025Review
- Role of DNA methylation and non‑coding RNAs expression in pathogenesis, detection, prognosis, and therapy‑resistant ovarian carcinoma (Review).Molecular medicine reports · 2025Review
- Repurposing ProTAME for Bladder Cancer: A Combined Therapeutic Approach Targeting Cell Migration and MMP Regulation.Biology · 2025Article
- Clinical relevance of PLK1 in epithelial ovarian cancer.Frontiers in pharmacology · 2025Review
- Review
- S-72, a Novel Orally Available Tubulin Inhibitor, Overcomes Paclitaxel Resistance via Inactivation of the STING Pathway in Breast Cancer.Pharmaceuticals (Basel, Switzerland) · 2023Article
- Targeting the anaphase-promoting complex/cyclosome (APC/C) enhanced antiproliferative and apoptotic response in bladder cancer.Saudi journal of biological sciences · 2023Article
- Chromosomal Instability as Enabling Feature and Central Hallmark of Breast Cancer.Breast cancer (Dove Medical Press) · 2023Review
- Sequential Targeting of PLK1 and PARP1 Reverses the Resistance to PARP Inhibitors and Enhances Platin-Based Chemotherapy in BRCA-Deficient High-Grade Serous Ovarian Cancer with KRAS Amplification.International journal of molecular sciences · 2022Article
- The Role of the APC/C and Its Coactivators Cdh1 and Cdc20 in Cancer Development and Therapy.Frontiers in genetics · 2022Review
- Onvansertib and paclitaxel combined in platinum-resistant ovarian carcinomas.Therapeutic advances in medical oncology · 2022Article
- Molecular response to PARP1 inhibition in ovarian cancer cells as determined by mass spectrometry based proteomics.Journal of ovarian research · 2021Article
- The Growth Suppression Activity of Diosmin and PGV-1 Co-Treatment on 4T1 Breast Cancer Targets Mitotic Regulatory Proteins.Asian Pacific journal of cancer prevention : APJCP · 2021Article
- Mitotic checkpoint defects: en route to cancer and drug resistance.Chromosome research : an international journal on the molecular, supramolecular and evolutionary aspects of chromosome biology · 2021Review
- Review
- Article
- Targeting mitotic exit in solid tumors.American journal of cancer research · 2021Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Paclitaxel is a frontline drug for the treatment of epithelial ovarian cancer (EOC). However, following paclitaxel-platinum based chemotherapy, tumor recurrence occurs in most ovarian cancer patients. Chromosomal instability (CIN) is a hallmark of cancer and represents genetic variation fueling tumor adaptation to cytotoxic effects of anticancer drugs. In this study, our Kaplan-Meier analysis including 263 ovarian cancer patients (stages I/II) revealed that high Polo-like kinase (PLK) 1 expression correlates with bad prognosis. To evaluate the role of PLK1 as potential cancer target within a combinatorial trial, we induced strong mitotic arrest in ovarian cancer cell lines by synergistically co-targeting microtubules (paclitaxel) and PLK1 (BI6727) followed by pharmaceutical inhibition of the Anaphase-Promoting Complex (APC/C) using proTAME. In short- and long-term experiments, this triple treatment strongly activated apoptosis in cell lines and primary ovarian cells derived from cancer patients. Mechanistically, BI6727/paclitaxel/proTAME stabilize Cyclin B1 and trigger mitotic arrest, which initiates mitochondrial apoptosis by inactivation of antiapoptotic BCL-2 family proteins, followed by activation of caspase-dependent effector pathways. This triple treatment prevented endoreduplication and reduced CIN, two mechanisms that are associated with aggressive tumors and the acquisition of drug resistance. This "two-punch strategy" (strong mitotic arrest followed by blocking mitotic exit) has important implications for developing paclitaxel-based combinatorial treatments in ovarian cancer.
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