ArticleInternational journal of molecular sciences2022
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.
Article in International journal of molecular sciences, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 13 citations in OpenAlex.
- Evaluating carboplatin and PARP inhibitor combination efficacy using high-grade serous carcinoma spheroids and organoids.Cancer biology & therapy · 2026Article
- Expanding Synthetic Lethality in DNA Damage Response-Defective Cancers Through Stress Phenotype-Guided Kinase Targeting.International journal of molecular sciences · 2026Review
- KRAS signaling networks, mutational heterogeneity, and emerging therapeutic strategies for cancer treatment.Biomarker research · 2026Review
- Ovarian Cancer Susceptibility and Chemosensitivity to KRAS Modulation.International journal of molecular sciences · 2026Article
- MLN0905 effectively kills gemcitabine-resistant pancreatic cancer cells by targeting PLK1.European journal of medical research · 2025Article
- Cyclin E1 overexpression sensitizes ovarian cancer cells to WEE1 and PLK1 inhibition.Oncogene · 2025Article
- Article
- Unveiling drug resistance pathways in high-grade serous ovarian cancer(HGSOC): recent advances and future perspectives.Frontiers in immunology · 2025Review
- Clinical relevance of PLK1 in epithelial ovarian cancer.Frontiers in pharmacology · 2025Review
- Beyond HRD Status: Unraveling Genetic Variants Impacting PARP Inhibitor Sensitivity in Advanced Ovarian Cancer.Cancer research communications · 2024Article
- Onvansertib treatment overcomes olaparib resistance in high-grade ovarian carcinomas.Cell death & disease · 2024Article
- PARP Inhibitors and Proteins Interacting with SLX4.Cancers · 2023Review
- PLK1 and PARP positively correlate in Middle Eastern breast cancer and their combined inhibition overcomes PARP inhibitor resistance in triple negative breast cancer.Frontiers in oncology · 2023Article
- Diagnostics and treatment of ovarian cancer in the era of precision medicine - opportunities and challenges.Frontiers in oncology · 2023Review
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Ovarian cancer (OC) accounts for approximately 4% of cancer deaths in women worldwide and is the deadliest gynecologic malignancy. High-grade serous ovarian cancer (HGSOC) is the most predominant ovarian cancer, in which BRCA1/2 gene mutation ranges from 3 to 27%. PARP inhibitors (PARPi) have shown promising results as a synthetically lethal therapeutic approach for BRCA mutant and recurrent OC in clinical use. However, emerging data indicate that BRCA-deficient cancers may be resistant to PARPi, and the mechanisms of this resistance remain elusive. We found that amplification of KRAS likely underlies PARPi resistance in BRCA2-deficient HGSOC. Our data suggest that PLK1 inhibition restores sensitivity to PARPi in HGSOC with KRAS amplification. The sequential combination of PLK1 inhibitor (PLK1i) and PARPi drastically reduces HGSOC cell survival and increases apoptosis. Furthermore, we were able to show that a sequential combination of PLK1i and PARPi enhanced the cellular apoptotic response to carboplatin-based chemotherapy in KRAS-amplified resistant HGSOC cells and 3D spheroids derived from recurrent ovarian cancer patients. Our results shed new light on the critical role of PLK1 in reversing PARPi resistance in KRAS-amplified HGSOC, and offer a new therapeutic strategy for this class of ovarian cancer patients where only limited options currently exist.
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