ArticleCancer research2014
RPA inhibition increases replication stress and suppresses tumor growth.
Article in Cancer research, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers.
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Who cites it
50 citing papers in PubMed, 71 citations in OpenAlex.
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- Re-establishment of TAD boundary organization during DNA replication.bioRxiv : the preprint server for biology · 2026Article
- Construction of a Lysine Lactylation- and DNA Damage Repair-Related Gene Signature to Predict the Prognosis and Drug Sensitivity of Breast Cancer Patients.International journal of molecular sciences · 2026Article
- Exploring the role of protein homeostasis regulation in glycolysis in head and neck tumors.Human cell · 2026Review
- Clinicopathological and functional evaluation of replication protein A in epithelial ovarian cancers: A target validation study.Translational oncology · 2026Article
- LAP2α drives breast tumorigenesis by mitigating replication stress.Cell death & disease · 2026Article
- African swine fever virus pEP364R acts as an important inflammatory-inducing factor to activate NLRP3 inflammasome-mediated pyroptosis by regulating DDX3X.PLoS pathogens · 2026Article
- Targeting DNA repair mechanisms in cancer therapy: the role of small molecule DNA repair inhibitors.NAR cancer · 2025Review
- PRMT5 Identified as a Viable Target for Combination Therapy in Preclinical Models of Pancreatic Cancer.Biomolecules · 2025Article
- Real-time genome imaging of host interactions in adeno-associated virus genome release.iScience · 2025Article
- Inhibition of RPA32 and Cytotoxic Effects of the Carnivorous PlantPlants (Basel, Switzerland) · 2025Article
- Targeting DNA damage sensors for cancer therapy.DNA repair · 2025Review
- The PARP1 selective inhibitor saruparib (AZD5305) elicits potent and durable antitumor activity in patient-derived BRCA1/2-associated cancer models.Genome medicine · 2024Article
- The effect of replication protein A inhibition and post-translational modification on ATR kinase signaling.Scientific reports · 2024Article
- The Effect of Replication Protein A Inhibition and Post-Translational Modification on ATR Kinase Signaling.Research square · 2024Article
- A perspective on tumor radiation resistance following high-LET radiation treatment.Journal of cancer research and clinical oncology · 2024Review
- Cytotoxicity and Multi-Enzyme Inhibition ofPlants (Basel, Switzerland) · 2024Article
- Article
- Targeting RPA promotes autophagic flux and the antitumor response to radiation in nasopharyngeal carcinoma.Journal of translational medicine · 2023Article
- Chemical Inhibition of RPA by HAMNO Alters Cell Cycle Dynamics by Impeding DNA Replication and G2-to-M Transition but Has Little Effect on the Radiation-Induced DNA Damage Response.International journal of molecular sciences · 2023Article
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
The ATR/Chk1 pathway is a critical surveillance network that maintains genomic integrity during DNA replication by stabilizing the replication forks during normal replication to avoid replication stress. One of the many differences between normal cells and cancer cells is the amount of replication stress that occurs during replication. Cancer cells with activated oncogenes generate increased levels of replication stress. This creates an increased dependency on the ATR/Chk1 pathway in cancer cells and opens up an opportunity to preferentially kill cancer cells by inhibiting this pathway. In support of this idea, we have identified a small molecule termed HAMNO ((1Z)-1-[(2-hydroxyanilino)methylidene]naphthalen-2-one), a novel protein interaction inhibitor of replication protein A (RPA), a protein involved in the ATR/Chk1 pathway. HAMNO selectively binds the N-terminal domain of RPA70, effectively inhibiting critical RPA protein interactions that rely on this domain. HAMNO inhibits both ATR autophosphorylation and phosphorylation of RPA32 Ser33 by ATR. By itself, HAMNO treatment creates DNA replication stress in cancer cells that are already experiencing replication stress, but not in normal cells, and it acts synergistically with etoposide to kill cancer cells in vitro and slow tumor growth in vivo. Thus, HAMNO illustrates how RPA inhibitors represent candidate therapeutics for cancer treatment, providing disease selectivity in cancer cells by targeting their differential response to replication stress. Cancer Res; 74(18); 5165-72. ©2014 AACR.
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