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Targeting the Cell Cycle, RRM2 and NF-κB for the Treatment of Breast Cancers.
Cancers (Basel)
February 2024
Department of Physiology and Pharmacology, Thomas J. Long School of Pharmacy, University of the Pacific, Stockton, CA 95211, USA.
A hallmark of cancer is the dysregulation of the cell cycle. The CDK4/6 inhibitor palbociclib is approved for treating advanced estrogen-receptor-positive breast cancer, but its success is limited by the development of acquired resistance owing to long-term therapy despite promising clinical outcomes. This situation necessitates the development of potential combination strategies.
View Article and Find Full Text PDFHepatitis C Virus Down-Regulates the Expression of Ribonucleotide Reductases to Promote Its Replication.
Pathogens
June 2023
Department of Biochemistry, School of Medicine, Tzu Chi University, Hualien 97004, Taiwan.
Ribonucleotide reductases (RRs or RNRs) catalyze the reduction of the OH group on the 2nd carbon of ribose, reducing four ribonucleotides (NTPs) to the corresponding deoxyribonucleotides (dNTPs) to promote DNA synthesis. Large DNA viruses, such as herpesviruses and poxviruses, could benefit their replication through increasing dNTPs via expression of viral RRs. Little is known regarding the relationship between cellular RRs and RNA viruses.
View Article and Find Full Text PDFSynergistic anticancer activity of combined ATR and ribonucleotide reductase inhibition in Ewing's sarcoma cells.
J Cancer Res Clin Oncol
September 2023
Department of Paediatric and Adolescent Medicine, Jena University Hospital, Friedrich Schiller University Jena, Am Klinikum 1, 07747, Jena, Germany.
Purpose: Ewing's sarcoma is a highly malignant childhood tumour whose outcome has hardly changed over the past two decades despite numerous attempts at chemotherapy intensification. It is therefore essential to identify new treatment options. The present study was conducted to explore the effectiveness of combined inhibition of two promising targets, ATR and ribonucleotide reductase (RNR), in Ewing's sarcoma cells.
View Article and Find Full Text PDFRRM2 Alleviates Doxorubicin-Induced Cardiotoxicity through the AKT/mTOR Signaling Pathway.
Biomolecules
February 2022
Department of Cardiology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, 160 Pujian Road, Shanghai 200127, China.
Doxorubicin (DOX) is an effective chemotherapeutic agent that plays an unparalleled role in cancer treatment. However, its serious dose-dependent cardiotoxicity, which eventually contributes to irreversible heart failure, has greatly limited the widespread clinical application of DOX. A previous study has demonstrated that the ribonucleotide reductase M2 subunit (RRM2) exerts salutary effects on promoting proliferation and inhibiting apoptosis and autophagy.
View Article and Find Full Text PDFMolecular Targeting of RRM2, NF-κB, and Mutant TP53 for the Treatment of Triple-Negative Breast Cancer.
Mol Cancer Ther
April 2021
Department of Physiology and Pharmacology, Thomas J. Long School of Pharmacy, University of the Pacific, Stockton, California.
Doxorubicin and other anthracycline derivatives are frequently used as part of the adjuvant chemotherapy regimen for triple-negative breast cancer (TNBC). Although effective, doxorubicin is known for its off-target and toxic side effect profile, particularly with respect to the myocardium, often resulting in left ventricular (LV) dysfunction and congestive heart failure when used at cumulative doses exceeding 400 mg/m Previously, we have observed that the ribonucleotide reductase subunit M2 (RRM2) is significantly overexpressed in estrogen receptor (ER)-negative cells as compared with ER-positive breast cancer cells. Here, we inhibited RRM2 in ER-negative breast cancer cells as a target for therapy in this difficult-to-treat population.
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