ArticleJournal of experimental & clinical cancer research : CR2019
New markers for human ovarian cancer that link platinum resistance to the cancer stem cell phenotype and define new therapeutic combinations and diagnostic tools.
Article in Journal of experimental & clinical cancer research : CR, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers, 1 of them a synthesis that pooled it.
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Who cites it
22 citing papers in PubMed, 1 synthesis or guideline pooled it, 40 citations in OpenAlex.
- Functional Gene Expression Differentiation of the Notch Signaling Pathway in Female Reproductive Tract Tissues-A Comprehensive Review With Analysis.Frontiers in cell and developmental biology · 2020Pooled it
- HOOK2 downregulation compromises the tumorigenic and stemness properties of ovarian cancer cells by increasing endoplasmic reticulum stress.Cell death & disease · 2026Article
- Novel Cross-Cancer Hub Genes in Doxorubicin Resistance Identified by Transcriptional Mapping.Biomedicines · 2025Article
- Therapeutic and Prognostic Relevance of Cancer Stem Cell Populations in Endometrial Cancer: A Narrative Review.Diagnostics (Basel, Switzerland) · 2025Review
- Artificial intelligence in ovarian cancer drug resistance advanced 3PM approach: subtype classification and prognostic modeling.The EPMA journal · 2024Article
- Protein homeostasis maintained by HOOK1 levels promotes the tumorigenic and stemness properties of ovarian cancer cells through reticulum stress and autophagy.Journal of experimental & clinical cancer research : CR · 2024Article
- Drug resistance in ovarian cancer: from mechanism to clinical trial.Molecular cancer · 2024Review
- Essential role of PLD2 in hypoxia-induced stemness and therapy resistance in ovarian tumors.Journal of experimental & clinical cancer research : CR · 2024Article
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- CCT2 prevented β-catenin proteasomal degradation to sustain cancer stem cell traits and promote tumor progression in epithelial ovarian cancer.Molecular biology reports · 2024Article
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- Leveraging Genomics, Transcriptomics, and Epigenomics to Understand the Biology and Chemoresistance of Ovarian Cancer.Cancers · 2021Review
- Mitogen signal-associated pathways, energy metabolism regulation, and mediation of tumor immunogenicity play essential roles in the cellular response of malignant pleural mesotheliomas to platinum-based treatment: a retrospective study.Translational lung cancer research · 2021Article
- Targeting cancer stem cells for reversing therapy resistance: mechanism, signaling, and prospective agents.Signal transduction and targeted therapy · 2021Review
- Notch signaling in female cancers: a multifaceted node to overcome drug resistance.Cancer drug resistance (Alhambra, Calif.) · 2021Review
- Design, synthesis and biological evaluation of 2-quinolyl-1,3-tropolone derivatives as new anti-cancer agents.RSC advances · 2021Article
- Chemoresistance-associated alternative splicing signatures in serous ovarian cancer.Oncology letters · 2020Article
- Review
- Article
- Downregulation of MYPT1 increases tumor resistance in ovarian cancer by targeting the Hippo pathway and increasing the stemness.Molecular cancer · 2020Article
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Authors and funding
15 authors at 5 institutions in 1 country.
Funding
Abstract
backgroundOvarian cancer is the leading cause of gynecologic cancer-related death, due in part to a late diagnosis and a high rate of recurrence. Primary and acquired platinum resistance is related to a low response probability to subsequent lines of treatment and to a poor survival. Therefore, a comprehensive understanding of the mechanisms that drive platinum resistance is urgently needed.
methodsWe used bioinformatics analysis of public databases and RT-qPCR to quantitate the relative gene expression profiles of ovarian tumors. Many of the dysregulated genes were cancer stem cell (CSC) factors, and we analyzed its relation to therapeutic resistance in human primary tumors. We also performed clustering and in vitro analyses of therapy cytotoxicity in tumorspheres.
resultsUsing bioinformatics analysis, we identified transcriptional targets that are common endpoints of genetic alterations linked to platinum resistance in ovarian tumors. Most of these genes are grouped into 4 main clusters related to the CSC phenotype, including the DNA damage, Notch and C-KIT/MAPK/MEK pathways. The relative expression of these genes, either alone or in combination, is related to prognosis and provide a connection between platinum resistance and the CSC phenotype. However, the expression of the CSC-related markers was heterogeneous in the resistant tumors, most likely because there were different CSC pools. Furthermore, our in vitro results showed that the inhibition of the CSC-related targets lying at the intersection of the DNA damage, Notch and C-KIT/MAPK/MEK pathways sensitize CSC-enriched tumorspheres to platinum therapies, suggesting a new option for the treatment of patients with platinum-resistant ovarian cancer.
conclusionsThe current study presents a new approach to target the physiology of resistant ovarian tumor cells through the identification of core biomarkers. We hypothesize that the identified mutations confer platinum resistance by converging to activate a few pathways and to induce the expression of a few common, measurable and targetable essential genes. These pathways include the DNA damage, Notch and C-KIT/MAPK/MEK pathways. Finally, the combined inhibition of one of these pathways with platinum treatment increases the sensitivity of CSC-enriched tumorspheres to low doses of platinum, suggesting a new treatment for ovarian cancer.
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