ArticleOncotarget2017
Refractory testicular germ cell tumors are highly sensitive to the second generation DNA methylation inhibitor guadecitabine.
Article in Oncotarget, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
45 citing papers in PubMed, 1 synthesis or guideline pooled it, 72 citations in OpenAlex.
- Incorporating DNA Methyltransferase Inhibitors (DNMTis) in the Treatment of Genitourinary Malignancies: A Systematic Review.Targeted oncology · 2018Pooled it
- Phase I Trial of DNA Methyltransferase Inhibitor Guadecitabine Combined with Cisplatin and Gemcitabine for Solid Malignancies Including Urothelial Carcinoma (SPIRE).Clinical cancer research : an official journal of the American Association for Cancer Research · 2021Trial
- 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
- MicroRNAs and immunotherapy in testicular germ cell tumors: opportunities and challenges for modulation of the immune microenvironment.Frontiers in immunology · 2026Review
- Treatment options in platinum-refractory male germ cell cancers: current standards and future directions.Therapeutic advances in medical oncology · 2026Review
- Driving precision medicine in testicular germ cell tumors: from preclinical models to clinical applications.Therapeutic advances in medical oncology · 2026Review
- Epithelial‑mesenchymal plasticity and cisplatin resistance in germ cell tumors: Mechanisms and emerging therapeutic strategies (Review).International journal of oncology · 2025Review
- Identification of novel susceptibility loci for testicular germ cell tumors through multi-omics analysis.Discover oncology · 2025Article
- Modeling of cancer stem cells and the tumor microenvironment Via NT2/D1 cells to probe pathology and treatment for cancer and beyond.Discover oncology · 2025Review
- Mechanisms of cisplatin sensitivity and resistance in testicular germ cell tumors and potential therapeutic agents (Review).Experimental and therapeutic medicine · 2025Review
- Refractory testicular germ cell tumors are highly sensitive to the targeting of polycomb pathway demethylases KDM6A and KDM6B.Cell communication and signaling : CCS · 2024Article
- Rewriting cellular fate: epigenetic interventions in obesity and cellular programming.Molecular medicine (Cambridge, Mass.) · 2024Review
- Children's Oncology Group's 2023 blueprint for research: Germ cell tumors.Pediatric blood & cancer · 2023Article
- Spectrum of Germ Cell Tumor (GCT): 5 Years' Experience in a Tertiary Care Center and Utility of OCT4 as a Diagnostic Adjunct.Indian journal of surgical oncology · 2022Article
- Overcoming Chemotherapy Resistance in Germ Cell Tumors.Biomedicines · 2022Review
- Reciprocal epigenetic remodeling controls testicular cancer hypersensitivity to hypomethylating agents and chemotherapy.Molecular oncology · 2022Article
- Epigenetics and Testicular Cancer: Bridging the Gap Between Fundamental Biology and Patient Care.Frontiers in cell and developmental biology · 2022Review
- Hypermethylation and global remodelling of DNA methylation is associated with acquired cisplatin resistance in testicular germ cell tumours.Epigenetics · 2021Article
- Resistance to Targeted Therapy and RASSF1A Loss in Melanoma: What Are We Missing?International journal of molecular sciences · 2021Review
- Differential methylation EPIC analysis discloses cisplatin-resistance related hypermethylation and tumor-specific heterogeneity within matched primary and metastatic testicular germ cell tumor patient tissue samples.Clinical epigenetics · 2021Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
17 authors at 6 institutions in 1 country.
Funding
Abstract
Testicular germ cell tumors (TGCTs) are the most common cancers of young males. A substantial portion of TGCT patients are refractory to cisplatin. There are no effective therapies for these patients, many of whom die from progressive disease. Embryonal carcinoma (EC) are the stem cells of TGCTs. In prior in vitro studies we found that EC cells were highly sensitive to the DNA methyltransferase inhibitor, 5-aza deoxycytidine (5-aza). Here, as an initial step in bringing demethylation therapy to the clinic for TGCT patients, we evaluated the effects of the clinically optimized, second generation demethylating agent guadecitabine (SGI-110) on EC cells in an animal model of cisplatin refractory testicular cancer. EC cells were exquisitely sensitive to guadecitabine and the hypersensitivity was dependent on high levels of DNA methyltransferase 3B. Guadecitabine mediated transcriptional reprogramming of EC cells included induction of p53 targets and repression of pluripotency genes. As a single agent, guadecitabine completely abolished progression and induced complete regression of cisplatin resistant EC xenografts even at doses well below those required to impact somatic solid tumors. Low dose guadecitabine also sensitized refractory EC cells to cisplatin in vivo. Genome-wide analysis indicated that in vivo antitumor activity was associated with activation of p53 and immune-related pathways and the antitumor effects of guadecitabine were dependent on p53, a gene rarely mutated in TGCTs. These preclinical findings suggest that guadecitabine alone or in combination with cisplatin is a promising strategy to treat refractory TGCT patients.
Indexed as
Identifiers
What OpenQuestion holds
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.