ArticleClinical cancer research : an official journal of the American Association for Cancer Research2019
A Novel Mechanism Driving Poor-Prognosis Prostate Cancer: Overexpression of the DNA Repair Gene, Ribonucleotide Reductase Small Subunit M2 (RRM2).
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 96 papers, 1 of them a synthesis that pooled it.
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Who cites it
96 citing papers in PubMed, 1 synthesis or guideline pooled it, 167 citations in OpenAlex.
- ERCC1 rs11615 polymorphism and chemosensitivity to platinum drugs in patients with ovarian cancer: a systematic review and meta-analysis.Journal of ovarian research · 2021Pooled it
- From epigenetics to metastasis: Multifaceted roles of lncRNAs in gastric cancer.Biochemistry and biophysics reports · 2026Review
- Adaptive Regulation of dNTP Homeostasis Confers Osimertinib Resistance in EGFR-Mutant Non-Small Cell Lung Carcinoma.Cancer research · 2026Article
- Hierarchies of resistance to DNA damage response inhibitors: from pathway restoration to replication stress tolerance.Experimental hematology & oncology · 2026Review
- Decreased expression of ribonucleotide reductase M2 accelerates ovarian aging by suppressing cell proliferation and inducing DNA damage in mouse theca-interstitial cells.Journal of ovarian research · 2026Article
- Erianin facilitates pyroptosis in endometrial cancer via targeting m6A reader YTHDF1.Chinese medicine · 2026Article
- Integrative high-throughput studies to develop novel targets and drugs for the treatment of advanced prostate cancer.Genes & diseases · 2026Article
- Targeting replication stress in neuroblastoma by exploiting the synergistic potential of second generation RRM2 and CHK1 inhibitors.Cell death & disease · 2026Article
- Multi omics network toxicology andFrontiers in cell and developmental biology · 2026Article
- Unravelling TPX2-centered co-expression networks as key drivers of aggressive prostate cancer.Scientific reports · 2025Article
- The evolving landscape of antibody-drug conjugates (ADCs) for treatment of prostate cancer.NPJ precision oncology · 2025Review
- Targeting RRM2 with dual-modal theranostic smart nanoresponder overcomes osimertinib resistance and triggers immune remodeling in NSCLC.Science advances · 2025Article
- Dynamic shifts in trophoblast nucleos(t)ide metabolism, transport, and adenosine signaling during gestation and preterm birth.Scientific reports · 2025Article
- FUBP3: A new player in HIV-1 transcriptional activation and immune regulation.Molecular therapy. Nucleic acids · 2025Article
- Unveiling the Therapeutic Potential of Targeting RRM2 in Hepatocellular Carcinoma: An Integrated In Silico and In Vitro Study.Functional & integrative genomics · 2025Article
- Ribonucleotide-diphosphate reductase subunit M2 (RRM2) expression and colorectal cancer invasiveness: a potential prognostic biomarker.Molecular biology reports · 2025Article
- Development of a prognostic model based on immunogenic cell death/ferroptosis-related genes and the study of TREX1 effects on prostate cancer cells.Frontiers in immunology · 2025Article
- Developing a prognostic stratification model based on glutathione metabolism in thyroid cancer and validating RRM2's tumor-promoting role.Frontiers in oncology · 2025Article
- RRM2 promotes liver metastasis of pancreatic cancer by stabilizing YBX1 and activating the TGF-beta pathway.iScience · 2024Article
- Article
36 more citing papers are in PubMed but not listed here.
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Authors and funding
21 authors at 6 institutions in 4 countries.
Funding
Abstract
purposeDefects in genes in the DNA repair pathways significantly contribute to prostate cancer progression. We hypothesize that overexpression of DNA repair genes may also drive poorer outcomes in prostate cancer. The ribonucleotide reductase small subunit M2 (RRM2) is essential for DNA synthesis and DNA repair by producing dNTPs. It is frequently overexpressed in cancers, but very little is known about its function in prostate cancer. EXPERIMENTAL
designThe oncogenic activity of RRM2 in prostate cancer cells was assessed by inhibiting or overexpressing RRM2. The molecular mechanisms of RRM2 function were determined. The clinical significance of RRM2 overexpression was evaluated in 11 prostate cancer clinical cohorts. The efficacy of an RRM2 inhibitor (COH29) was assessed
resultsKnockdown of RRM2 inhibited its oncogenic function, whereas overexpression of RRM2 promoted epithelial mesenchymal transition in prostate cancer cells. The prognostic value of RRM2 RNA levels in prostate cancer was confirmed in 11 clinical cohorts. Integrating the transcriptomic and phosphoproteomic changes induced by RRM2 unraveled multiple oncogenic pathways downstream of RRM2. Targeting RRM2 with COH29 showed excellent efficacy. Thirteen putative RRM2-targeting transcription factors were bioinformatically identified, and FOXM1 was validated to transcriptionally activate RRM2 in prostate cancer.
conclusionsWe propose that increased expression of RRM2 is a mechanism driving poor patient outcomes in prostate cancer and that its inhibition may be of significant therapeutic value.
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