ArticleCancers2021
Testicular Germ Cell Tumors Acquire Cisplatin Resistance by Rebalancing the Usage of DNA Repair Pathways.
Article in Cancers, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers, 1 of them a synthesis that pooled it.
What it found
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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
21 citing papers in PubMed, 1 synthesis or guideline pooled it, 25 citations in OpenAlex.
- Research progress on the role and mechanism of DNA damage repair in germ cell development.Frontiers in endocrinology · 2023Pooled it
- Olaparib as a rescue treatment in platinum-refractory germ-cell tumors: the IGG-02 phase II trial.ESMO open · 2025Trial
- Gemcitabine, carboplatin and veliparib in multiple relapsed/refractory germ cell tumours: The GCT-SK-004 phase II trial.Investigational new drugs · 2021Trial
- Molecular pathology of testicular germ cell tumours: an update for practicing pathologists.Histopathology · 2026Review
- Treatment options in platinum-refractory male germ cell cancers: current standards and future directions.Therapeutic advances in medical oncology · 2026Review
- Olaparib Response in a Patient With Platinum-Refractory Germ Cell Tumor Harboring a SomaticJCO precision oncology · 2026Article
- Mechanisms of cisplatin sensitivity and resistance in testicular germ cell tumors and potential therapeutic agents (Review).Experimental and therapeutic medicine · 2025Review
- RAS/Mitogen-Activated Protein Kinase Signaling Pathway in Testicular Germ Cell Tumors.Life (Basel, Switzerland) · 2024Review
- PARP inhibitors in testicular germ cell tumors: what we know and what we are looking for.Frontiers in genetics · 2024Review
- Genome-scale CRISPR screen reveals neddylation to contribute to cisplatin resistance of testicular germ cell tumours.British journal of cancer · 2023Article
- Effect of the PARP inhibitor veliparib on germ cell tumor cell lines.Oncology letters · 2022Article
- Testis-expressed gene 11 inhibits cisplatin-induced DNA damage and contributes to chemoresistance in testicular germ cell tumor.Scientific reports · 2022Article
- Review
- Multifaceted regulation and functions of 53BP1 in NHEJ‑mediated DSB repair (Review).International journal of molecular medicine · 2022Review
- Reciprocal epigenetic remodeling controls testicular cancer hypersensitivity to hypomethylating agents and chemotherapy.Molecular oncology · 2022Article
- Comprehensive characteristics of pathological subtypes in testicular germ cell tumor: Gene expression, mutation and alternative splicing.Frontiers in immunology · 2022Article
- The component of the mJournal of experimental & clinical cancer research : CR · 2021Article
- Non-Coding RNAs and Splicing Activity in Testicular Germ Cell Tumors.Life (Basel, Switzerland) · 2021Review
- Between a Rock and a Hard Place: An Epigenetic-Centric View of Testicular Germ Cell Tumors.Cancers · 2021Review
- Identification of mRNA Prognostic Markers for TGCT by Integration of Co-Expression and CeRNA Network.Frontiers in endocrinology · 2021Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 2 countries.
Funding
Abstract
Despite germ cell tumors (GCTs) responding to cisplatin-based chemotherapy at a high rate, a subset of patients does not respond to treatment and have significantly worse prognosis. The biological mechanisms underlying the resistance remain unknown. In this study, by using two TGCT cell lines that have acquired cisplatin resistance after chronic exposure to the drug, we identified some key proteins and mechanisms of acquired resistance. We show that cisplatin-resistant cell lines had a non-homologous end-joining (NHEJ)-less phenotype. This correlated with a reduced basal expression of TP53-binding protein 1 (53BP1) and DNA-dependent protein kinase (DNA-PKcs) proteins and reduced formation of 53BP1 foci after cisplatin treatment. Consistent with these observations, modulation of 53BP1 protein expression altered the cell line's resistance to cisplatin, and inhibition of DNA-PKcs activity antagonized cisplatin cytotoxicity. Dampening of NHEJ was accompanied by a functional increase in the repair of DNA double-strand breaks (DSBs) by the homologous recombination repair pathway. As a result, cisplatin-resistant cells were more resistant to PARP inhibitor (PARPi) monotherapy. Moreover, when PARPi was given in combination with cisplatin, it exerted an additive/synergistic effect, and reduced the cisplatin dose for cytotoxicity. These results suggest that treatment of cisplatin-refractory patients may benefit from low-dose cisplatin therapy combined with PARPi.
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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.