The DOI matches its Crossref record; 55 of the 56 references it cites were found in a registry or an index.
Epigenetic Resensitization to Platinum in Ovarian Cancer
Open accessPublished version of a preprint
Abstract
Preclinical studies have shown that hypomethylating agents reverse platinum resistance in ovarian cancer. In this phase II clinical trial, based upon the results of our phase I dose defining study, we tested the clinical and biologic activity of low-dose decitabine administered before carboplatin in platinum-resistant ovarian cancer patients. Among 17 patients with heavily pretreated and platinum-resistant ovarian cancer, the regimen induced a 35% objective response rate (RR) and progression-free survival (PFS) of 10.2 months, with nine patients (53%) free of progression at 6 months. Global and gene-specific DNA demethylation was achieved in peripheral blood mononuclear cells and tumors. The number of demethylated genes was greater (P < 0.05) in tumor biopsies from patients with PFS more than 6 versus less than 6 months (311 vs. 244 genes). Pathways enriched at baseline in tumors from patients with PFS more than 6 months included cytokine–cytokine receptor interactions, drug transporters, and mitogen-activated protein kinase, toll-like receptor and Jak-STAT signaling pathways, whereas those enriched in demethylated genes after decitabine treatment included pathways involved in cancer, Wnt signaling, and apoptosis (P < 0.01). Demethylation of MLH1, RASSF1A, HOXA10, and HOXA11 in tumors positively correlated with PFS (P < 0.05). Together, the results of this study suggest that low-dose decitabine altered DNA methylation of genes and cancer pathways, restoring sensitivity to carboplatin in patients with heavily pretreated ovarian cancer and resulting in a high RR and prolonged PFS. Cancer Res; 72(9); 2197–205. ©2012 AACR.
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Metadata
- Authors
- Matei, D., Fang, F., Shen, C., Schilder, J., Arnold, A., Zeng, Y., Berry, W. A., Huang, T., & Nephew, K. P.
- Affiliations
- Indiana University Health (US)
- Corresponding author
- Matei, Daniela
- Nephew, Kenneth P.
- ORCID
- Venue
- Cancer Research
- Published
- 2012-04-30
- Volume
- 72
- Issue
- 9
- Pages
- 2197-2205
- ISSN
- 0008-5472 (ISSN-L)
- 1538-7445
- PMC
- PMC3700422
- OpenAlex
- W2151783390
- Cited by
- 390
- References
- 56
- Citations by year
- 2026: 20 · 2025: 11 · 2024: 27 · 2023: 23 · 2022: 21 · 2021: 33 · 2020: 21 · 2019: 38 · 2018: 36 · 2017: 33 · 2016: 35 · 2015: 39 · 2014: 32 · 2013: 18 · 2012: 3
- FWCI
- 34.25
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Cancer Research (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- IUScholarWorks (Indiana University) (submittedVersion)
- Funders
- U.S. Food and Drug Administration
- National Cancer Institute (CA113001, R21CA133877, R01CA085289, U54CA113001, CA133877)
- Topics
- Health Sciences › Medicine › Oncology › Ovarian cancer diagnosis and treatment
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Health Sciences › Medicine › Oncology › Metal complexes synthesis and properties
- Keywords
- ovarian cancer, platinum resistance, decitabine, DNA demethylation, hypomethylating agents, carboplatin, progression-free survival, MLH1, RASSF1A, HOXA10, HOXA11, drug transporters, Wnt signaling, apoptosis, cytokine signaling pathways
- MeSH terms
- Decitabine, Aged, Aged, 80 and over, Antineoplastic Combined Chemotherapy Protocols, Azacitidine, Female, Humans, Middle Aged, Neoplasm Recurrence, Local, Ovarian Neoplasms, Peritoneal Neoplasms, Carboplatin, Disease-Free Survival, DNA Methylation
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