ArticleClinical cancer research : an official journal of the American Association for Cancer Research2020
DGKA Provides Platinum Resistance in Ovarian Cancer Through Activation of c-JUN-WEE1 Signaling.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 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
35 citing papers in PubMed, 1 synthesis or guideline pooled it, 60 citations in OpenAlex.
- An update of predictive biomarkers related to WEE1 inhibition in cancer therapy.Journal of cancer research and clinical oncology · 2024Pooled it
- Multi-omics analysis reveals the attenuation of the interferon pathway as a driver of chemo-refractory ovarian cancer.Cell reports. Medicine · 2025Trial
- Role of the tumor microenvironment in chemotherapy resistance in ovarian cancer and targeted therapy.Journal of ovarian research · 2025Review
- Lactate Enhances Non-Homologous End Joining Repair and Chemoresistance Through Facilitating XRCC4-LIG4 Complex Assembly in Ovarian Cancer.Biomedicines · 2025Article
- Simvastatin overcomes the pPCK1-pLDHA-SPRINGlac axis-mediated ferroptosis and chemo-immunotherapy resistance in AKT-hyperactivated intrahepatic cholangiocarcinoma.Cancer communications (London, England) · 2025Article
- High expression of DGKA indicates poor overall survival of nasopharyngeal carcinoma.Discover oncology · 2025Article
- CRISPR-Cas9 knockout of DGKα/ζ improves the anti-tumor activities of TAG-72 CAR-T cells in ovarian cancer.Molecular therapy. Oncology · 2025Article
- Regulation of nucleotide excision repair by wild-type HRAS signaling in head and neck cancer.Cancer gene therapy · 2025Article
- DGKα Enhances Tumorigenic Activity in Bladder Cancer Patients With Chronic Kidney Disease.Cancer medicine · 2025Article
- Exploring Metabolic Approaches for Epithelial Ovarian Cancer Therapy.Journal of cellular physiology · 2025Review
- WEE Family Kinase Inhibitors Combined with Sorafenib Can Selectively Inhibit HCC Cell Proliferation.Current cancer drug targets · 2025Article
- Galectin-1 Promotes Gastric Carcinoma Progression and Cisplatin Resistance Through the NRP-1/c-JUN/Wee1 Pathway.Journal of gastric cancer · 2024Article
- PLA2G4A and ACHE modulate lipid profiles via glycerophospholipid metabolism in platinum-resistant gastric cancer.Journal of translational medicine · 2024Article
- Suppression of ITPKB degradation by Trim25 confers TMZ resistance in glioblastoma through ROS homeostasis.Signal transduction and targeted therapy · 2024Article
- A Prognostic Model Based on Metabolism-Related Genes for Patients with Ovarian Cancer.Doklady. Biochemistry and biophysics · 2023Article
- Article
- Targeting diacylglycerol kinase α impairs lung tumorigenesis by inhibiting cyclin D3.Thoracic cancer · 2023Article
- ODF2L acts as a synthetic lethal partner with WEE1 inhibition in epithelial ovarian cancer models.The Journal of clinical investigation · 2023Article
- Inhibition of JNK/c-Jun-ATF2 Overcomes Cisplatin Resistance in Liver Cancer through down-Regulating Galectin-1.International journal of biological sciences · 2023Article
- Metabolic reprogramming of three major nutrients in platinum-resistant ovarian cancer.Frontiers in oncology · 2023Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 3 institutions in 2 countries.
Funding
Abstract
purposeAlthough platinum compounds are the first-line treatment for ovarian cancer, the majority of patients relapse and develop resistance to treatment. However, the mechanism underlying resistance is unclear. The goal of our study is to decipher the mechanism by which a metabolic kinase, diacylglycerol kinase alpha (DGKA), confers platinum resistance in ovarian cancer. EXPERIMENTAL
designMetabolic kinase RNAi synthetic lethal screening was used to identify a cisplatin resistance driver in ovarian cancer. DGKA variants were used to demonstrate the need for DGKA activity in cisplatin resistance. Phospho-proteomic and genomic screens were performed to identify downstream effectors of DGKA. Therapeutic efficacy of targeting DGKA was confirmed and clinical relevance of DGKA signaling was validated using ovarian cancer patient-derived tumors that had different responses to platinum-based therapy.
resultsWe found that platinum resistance was mediated by DGKA and its product, phosphatidic acid (PA), in ovarian cancer. Proteomic and genomic screens revealed that DGKA activates the transcription factor c-JUN and consequently enhances expression of a cell-cycle regulator, WEE1. Mechanistically, PA facilitates c-JUN N-terminal kinase recruitment to c-JUN and its nuclear localization, leading to c-JUN activation upon cisplatin exposure. Pharmacologic inhibition of DGKA sensitized ovarian cancer cells to cisplatin treatment and DGKA-c-JUN-WEE1 signaling positively correlated with platinum resistance in tumors derived from patients with ovarian cancer.
conclusionsOur study demonstrates how the DGKA-derived lipid messenger, PA, contributes to cisplatin resistance by intertwining with kinase and transcription networks, and provides preclinical evidence for targeting DGKA as a new strategy in ovarian cancer treatment to battle cisplatin resistance.
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.