ArticleClinical cancer research : an official journal of the American Association for Cancer Research2014
The novel, small-molecule DNA methylation inhibitor SGI-110 as an ovarian cancer chemosensitizer.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 67 papers, 1 of them a synthesis that pooled it.
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Who cites it
67 citing papers in PubMed, 1 synthesis or guideline pooled it, 98 citations in OpenAlex.
- Incorporating DNA Methyltransferase Inhibitors (DNMTis) in the Treatment of Genitourinary Malignancies: A Systematic Review.Targeted oncology · 2018Pooled it
- A Randomized Phase II Trial of Epigenetic Priming with Guadecitabine and Carboplatin in Platinum-resistant, Recurrent Ovarian Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2020Trial
- Cancer stem cells: landscape, challenges and emerging therapeutic innovations.Signal transduction and targeted therapy · 2025Review
- Stochastic demethylation and redundant epigenetic suppressive mechanisms generate highly heterogeneous responses to pharmacological DNA methyltransferase inhibition.Journal of experimental & clinical cancer research : CR · 2025Article
- The therapeutic potential of targeting the CHD protein family in cancer.Pharmacology & therapeutics · 2024Review
- Preclinical Evaluation of NTX-301, a Novel DNA Hypomethylating Agent in Ovarian Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2024Article
- Prediction of Chemoresistance-How Preclinical Data Could Help to Modify Therapeutic Strategy in High-Grade Serous Ovarian Cancer.Current oncology (Toronto, Ont.) · 2023Review
- DNA Methyltransferase 1 Targeting Using Guadecitabine Inhibits Prostate Cancer Growth by an Apoptosis-Independent Pathway.Cancers · 2023Article
- The role of DNA methylation in ovarian cancer chemoresistance: A narrative review.Health science reports · 2023Article
- A Novel ALDH1A1 Inhibitor Blocks Platinum-Induced Senescence and Stemness in Ovarian Cancer.Cancers · 2022Article
- Platinum-induced mitochondrial OXPHOS contributes to cancer stem cell enrichment in ovarian cancer.Journal of translational medicine · 2022Article
- Revisiting chemoresistance in ovarian cancer: Mechanism, biomarkers, and precision medicine.Genes & diseases · 2022Review
- DNA Methylation Malleability and Dysregulation in Cancer Progression: Understanding the Role of PARP1.Biomolecules · 2022Review
- Article
- Platinum-resistant ovarian cancer: From drug resistance mechanisms to liquid biopsy-based biomarkers for disease management.Seminars in cancer biology · 2021Review
- Methylomic Signatures of High Grade Serous Ovarian Cancer.Epigenetics · 2021Article
- Ovarian cancer: epigenetics, drug resistance, and progression.Cancer cell international · 2021Review
- Targeting Ovarian Cancer Stem Cells by Dual Inhibition of HOTAIR and DNA Methylation.Molecular cancer therapeutics · 2021Article
- Resistance to Targeted Therapy and RASSF1A Loss in Melanoma: What Are We Missing?International journal of molecular sciences · 2021Review
- Molecular Targeted Therapy in Myelodysplastic Syndromes: New Options for Tailored Treatments.Cancers · 2021Review
7 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
16 authors at 2 institutions in 1 country.
Funding
Abstract
purposeTo investigate SGI-110 as a "chemosensitizer" in ovarian cancer and to assess its effects on tumor suppressor genes (TSG) and chemoresponsiveness-associated genes silenced by DNA methylation in ovarian cancer. EXPERIMENTAL
designSeveral ovarian cancer cell lines were used for in vitro and in vivo platinum resensitization studies. Changes in DNA methylation and expression levels of TSG and other cancer-related genes in response to SGI-110 were measured by pyrosequencing and RT-PCR.
resultsWe demonstrate in vitro that SGI-110 resensitized a range of platinum-resistant ovarian cancer cells to cisplatin (CDDP) and induced significant demethylation and reexpression of TSG, differentiation-associated genes, and putative drivers of ovarian cancer cisplatin resistance. In vivo, SGI-110 alone or in combination with CDDP was well tolerated and induced antitumor effects in ovarian cancer xenografts. Pyrosequencing analyses confirmed that SGI-110 caused both global (LINE1) and gene-specific hypomethylation in vivo, including TSGs (RASSF1A), proposed drivers of ovarian cancer cisplatin resistance (MLH1 and ZIC1), differentiation-associated genes (HOXA10 and HOXA11), and transcription factors (STAT5B). Furthermore, DNA damage induced by CDDP in ovarian cancer cells was increased by SGI-110, as measured by inductively coupled plasma-mass spectrometry analysis of DNA adduct formation and repair of cisplatin-induced DNA damage.
conclusionsThese results strongly support further investigation of hypomethylating strategies in platinum-resistant ovarian cancer. Specifically, SGI-110 in combination with conventional and/or targeted therapeutics warrants further development in this setting.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.