ArticleEBioMedicine2019
MYC status as a determinant of synergistic response to Olaparib and Palbociclib in ovarian cancer.
Article in EBioMedicine, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 59 papers.
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Who cites it
59 citing papers in PubMed, 111 citations in OpenAlex.
- Targeting histone deacetylation, cell cycle regulators and heat shock proteins as novel therapeutic strategies for penile cancers.NPJ precision oncology · 2026Article
- CDK4/6i reverse PARPi resistance by targeting the E2F1- MCM2/5 pathway.NPJ precision oncology · 2026Article
- Exploiting synthetic lethality in epithelial ovarian cancer: multi-dimensional approaches beyond DNA damage repair.Molecular cancer · 2026Review
- DNA damaging agents boost the transcription of endothelin A receptor in high-grade serous ovarian cancer.Journal of experimental & clinical cancer research : CR · 2025Article
- Review
- Harnessing transcriptional regulation of alternative end-joining to predict cancer treatment.NAR cancer · 2025Article
- EZH2 inhibition sensitizes MYC-high medulloblastoma cancers to PARP inhibition by regulating NUPR1-mediated DNA repair.Oncogene · 2025Article
- MYC and HSF1 Cooperate to Drive Sensitivity to Polo-like Kinase 1 Inhibitor Volasertib in High-grade Serous Ovarian Cancer.Cancer research communications · 2025Article
- Rethinking MYC inhibition: a multi-dimensional approach to overcome cancer's master regulator.Frontiers in cell and developmental biology · 2025Review
- Latest Advancements of Natural Products in Combating Ovarian Cancer.Journal of Cancer · 2025Review
- Biomimetic Targeted Co-Delivery System Engineered from Genomic Insights for Precision Treatment of Osteosarcoma.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- The CDK4/6 Inhibitor Palbociclib Induces Cell Senescence of High-grade Serous Ovarian Cancer Through Acetylation of p53.Biochemical genetics · 2024Article
- CDC7 Inhibition Potentiates Antitumor Efficacy of PARP Inhibitor in Advanced Ovarian Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Dual Targeting of CXCancers · 2024Article
- SGK1 suppresses ferroptosis in ovarian cancer via NRF2-dependent and -independent pathways.Oncogene · 2024Article
- Establishing the homologous recombination score threshold in metastatic prostate cancer patients to predict the efficacy of PARP inhibitors.Journal of the National Cancer Center · 2024Article
- Preclinical evaluation of CDK4 phosphorylation predicts high sensitivity of pleural mesotheliomas to CDK4/6 inhibition.Molecular oncology · 2024Article
- Inhibition of palmitoyltransferase ZDHHC12 sensitizes ovarian cancer cells to cisplatin through ROS-mediated mechanisms.Cancer science · 2024Article
- Article
- PARP inhibitors: enhancing efficacy through rational combinations.British journal of cancer · 2023Review
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Authors and funding
12 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundWhile PARP inhibitors and CDK4/6 inhibitors, the two classes of FDA-approved agents, have shown promising clinical benefits, there is an urgent need to develop new therapeutic strategies to improve clinical response. Meanwhile, extending the utility of these inhibitors beyond their respective molecularly defined cancer types is challenging and will likely require biomarkers predictive of treatment response especially when used in a combination drug development setting.
methodsThe effects of PARP inhibitor Olaparib and CDK4/6 inhibitor Palbociclib on ovarian cancer cells lines including those of high-grade serous histology were examined in vitro and in vivo. We investigated the molecular mechanism underlying the synergistic effects of drug combination.
findingsWe show for the first time that combining PARP and CDK4/6 inhibition has synergistic effects against MYC overexpressing ovarian cancer cells both in vitro and in vivo. Mechanistically, we find that Palbociclib induces homologous recombination (HR) deficiency through downregulation of MYC-regulated HR pathway genes, causing synthetic lethality with Olaparib. We further demonstrate that MYC expression determines sensitivity to combinatorial treatment with Olaparib and Palbociclib.
interpretationOur data provide a rationale for clinical evaluation of therapeutic synergy of these two classes of inhibitors in ovarian cancer patients whose tumors show high MYC expression and who do not respond to PARP inhibitors or CDK4/6 inhibitors monotherapies. FUND: This work was supported by the National Natural Science Foundation of China [81672575, 81874111, 81472447 to HC; 81572586 and 81372853 to PL], and the Liaoning Provincial Key Basic Research Program for Universities [LZ2017002 to HC].
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