ArticleMolecular cancer therapeutics2012
Deficient DNA damage signaling leads to chemoresistance to cisplatin in oral cancer.
Article in Molecular cancer therapeutics, 2012. 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.
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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.
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Who cites it
45 citing papers in PubMed, 1 synthesis or guideline pooled it.
- The role of PPM1D in cancer and advances in studies of its inhibitors.Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2020Pooled it
- Cisplatin resistance in oral squamous cell carcinoma: mechanisms, reversal strategies, and emerging technologies.Frontiers in physiology · 2026Review
- MiRNAs: main players of cancer drug resistance target ABC transporters.Naunyn-Schmiedeberg's archives of pharmacology · 2025Review
- Advances in Nanotechnology-Based Cisplatin Delivery for ORL Cancers: A Comprehensive Review.International journal of molecular sciences · 2025Review
- Hepatic artery infusion chemotherapy: A resurgence.World journal of gastrointestinal oncology · 2025Article
- Knockdown of IGF2BP2 overcomes cisplatin-resistance in lung cancer through downregulating Spon2 gene.Hereditas · 2024Article
- HNCDrugResDb: a platform for deciphering drug resistance in head and neck cancers.Scientific reports · 2024Article
- The Role of Endoplasmic Reticulum Stress on Reducing Recombinant Protein Production in Mammalian Cells.Biochemical engineering journal · 2024Article
- Cancer, metastasis, and the epigenome.Molecular cancer · 2024Review
- Syk-dependent homologous recombination activation promotes cancer resistance to DNA targeted therapy.Drug resistance updates : reviews and commentaries in antimicrobial and anticancer chemotherapy · 2024Article
- Molecular and cellular paradigms of multidrug resistance in cancer.Cancer reports (Hoboken, N.J.) · 2022Review
- Article
- Differential roles of the Wip1-p38-p53 DNA damage response pathway in early/advanced-stage ovarian clear cell carcinomas.World journal of surgical oncology · 2022Article
- CaCells · 2022Review
- The MASTL-ENSA-PP2A/B55 axis modulates cisplatin resistance in oral squamous cell carcinoma.Frontiers in cell and developmental biology · 2022Article
- Review
- PARP1 Upregulation in Recurrent Oral Cancer and Treatment Resistance.Frontiers in cell and developmental biology · 2021Article
- R2TP/PAQosome as a promising chemotherapeutic target in cancer.The Japanese dental science review · 2020Review
- Broccoli extract increases drug-mediated cytotoxicity towards cancer stem cells of head and neck squamous cell carcinoma.British journal of cancer · 2020Article
- Natural compounds as potential adjuvants to cancer therapy: Preclinical evidence.British journal of pharmacology · 2020Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors.
Funding
Abstract
Activation of the cellular DNA damage response (DDR) is an important determinant of cell sensitivity to cisplatin and other chemotherapeutic drugs that eliminate tumor cells through induction of DNA damage. It is therefore important to investigate whether alterations of the DNA damage-signaling pathway confer chemoresistance in cancer cells and whether pharmacologic manipulation of the DDR pathway can resensitize these cells to cancer therapy. In a panel of oral/laryngeal squamous cell carcinoma (SCC) cell lines, we observed deficiencies in DNA damage signaling in correlation with cisplatin resistance, but not with DNA repair. These deficiencies are consistent with reduced expression of components of the ataxia telangiectasia mutated (ATM)-dependent signaling pathway and, in particular, strong upregulation of Wip1, a negative regulator of the ATM pathway. Wip1 knockdown or inhibition enhanced DNA damage signaling and resensitized oral SCC cells to cisplatin. In contrast to the previously reported involvement of Wip1 in cancer, Wip1 upregulation and function in these SCC cells is independent of p53. Finally, using xenograft tumor models, we showed that Wip1 upregulation promotes tumorigenesis and its inhibition improves the tumor response to cisplatin. Thus, this study reveals that chemoresistance in oral SCCs is partially attributed to deficiencies in DNA damage signaling, and Wip1 is an effective drug target for enhanced cancer therapy.
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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.