ArticleInternational journal of molecular sciences2021
CX-5461 Enhances the Efficacy of APR-246 via Induction of DNA Damage and Replication Stress in Triple-Negative Breast Cancer.
Article in International journal of molecular sciences, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 24 citations in OpenAlex.
- Ensemble model for neoadjuvant chemotherapy response prediction and treatment sensitivity in TNBC based on DNA replication stress signatures.Scientific reports · 2025Article
- The G-quadruplex ligand CX-5461: an innovative candidate for disease treatment.Journal of translational medicine · 2025Review
- PRIMA-1ACS omega · 2023Article
- APR-246 Enhances Colorectal Cancer Sensitivity to Radiotherapy.Molecular cancer therapeutics · 2023Article
- Potential biomarkers uncovered by bioinformatics analysis in sotorasib resistant-pancreatic ductal adenocarcinoma.Frontiers in medicine · 2023Article
- CBL0137 impairs homologous recombination repair and sensitizes high-grade serous ovarian carcinoma to PARP inhibitors.Journal of experimental & clinical cancer research : CR · 2022Article
- Review
- Ribosome-Directed Therapies in Cancer.Biomedicines · 2022Review
- Review
- Targeting regulated cell death (RCD) with small-molecule compounds in triple-negative breast cancer: a revisited perspective from molecular mechanisms to targeted therapies.Journal of hematology & oncology · 2022Review
- Review
- Differential p53-Mediated Cellular Responses to DNA-Damaging Therapeutic Agents.International journal of molecular sciences · 2021Review
- G-quadruplex DNA: a novel target for drug design.Cellular and molecular life sciences : CMLS · 2021Review
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer lacking targeted therapy. Here, we evaluated the anti-cancer activity of APR-246, a P53 activator, and CX-5461, a RNA polymerase I inhibitor, in the treatment of TNBC cells. We tested the efficacy of individual and combination therapy of CX-5461 and APR-246 in vitro, using a panel of breast cancer cell lines. Using publicly available breast cancer datasets, we found that components of RNA Pol I are predominately upregulated in basal-like breast cancer, compared to other subtypes, and this upregulation is associated with poor overall and relapse-free survival. Notably, we found that the treatment of breast cancer cells lines with CX-5461 significantly hampered cell proliferation and synergistically enhanced the efficacy of APR-246. The combination treatment significantly induced apoptosis that is associated with cleaved PARP and Caspase 3 along with Annexin V positivity. Likewise, we also found that combination treatment significantly induced DNA damage and replication stress in these cells. Our data provide a novel combination strategy by utilizing APR-246 in combination CX-5461 in killing TNBC cells that can be further developed into more effective therapy in TNBC therapeutic armamentarium.
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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.