ArticleProceedings of the National Academy of Sciences of the United States of America2016
Phosphoinositide 3-kinase inhibitors induce DNA damage through nucleoside depletion.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 67 papers.
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Who cites it
67 citing papers in PubMed, 92 citations in OpenAlex.
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- Simultaneous inhibition of PARP/AKT to intercept nascent BRCA1/2NPJ breast cancer · 2026Article
- Integration of Whole-Genome Sequencing Analysis with Unique Patient-Derived Models Reveals Clinically Relevant Drug Targets in TFCP2 Fusion-Defined Rhabdomyosarcoma.Molecular cancer therapeutics · 2025Article
- Energy Deficiency-Induced ATG4B Nuclear Translocation Inhibits PRMT1-Mediated DNA Repair and Promotes Leukemia Progression.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
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- Nanoemulsion of myricetin enhances its anti-tumor activity in nude mice of triple-negative breast cancer xenografts.Frontiers in oncology · 2025Article
- NOS inhibition sensitizes metaplastic breast cancer to PI3K inhibition and taxane therapy via c-JUN repression.Nature communications · 2024Article
- Chemoresistance to additive PARP/PI3K dual inhibition in triple-negative breast cancer cell lines is associated with adaptive stem cell-like prevalence.bioRxiv : the preprint server for biology · 2024Article
- Transcriptome and Metabolome Analyses Provide Insight into the Glucose-Induced Adipogenesis in Porcine Adipocytes.Current issues in molecular biology · 2024Article
- β1 integrin mediates unresponsiveness to PI3Kα inhibition for radiochemosensitization of 3D HNSCC models.Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2024Article
- Integrative modeling uncovers p21-driven drug resistance and prioritizes therapies for PIK3CA-mutant breast cancer.NPJ precision oncology · 2024Article
- Article
- Regulation of PI3K signaling in cancer metabolism and PI3K-targeting therapy.Translational breast cancer research : a journal focusing on translational research in breast cancer · 2024Review
- The PI3K/Akt Pathway and Glucose Metabolism: A Dangerous Liaison in Cancer.International journal of biological sciences · 2024Review
- Emerging roles of nucleotide metabolism in cancer.Trends in cancer · 2023Review
- Review
- DHX9-mediated pathway contributes to the malignant phenotype of myelodysplastic syndromes.iScience · 2023Article
- Synergistic effect of combined PI3 kinase inhibitor and PARP inhibitor treatment on BCR/ABL1-positive acute lymphoblastic leukemia cells.International journal of hematology · 2023Article
7 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
16 authors at 6 institutions in 2 countries.
Funding
Abstract
We previously reported that combining a phosphoinositide 3-kinase (PI3K) inhibitor with a poly-ADP Rib polymerase (PARP)-inhibitor enhanced DNA damage and cell death in breast cancers that have genetic aberrations in BRCA1 and TP53. Here, we show that enhanced DNA damage induced by PI3K inhibitors in this mutational background is a consequence of impaired production of nucleotides needed for DNA synthesis and DNA repair. Inhibition of PI3K causes a reduction in all four nucleotide triphosphates, whereas inhibition of the protein kinase AKT is less effective than inhibition of PI3K in suppressing nucleotide synthesis and inducing DNA damage. Carbon flux studies reveal that PI3K inhibition disproportionately affects the nonoxidative pentose phosphate pathway that delivers Rib-5-phosphate required for base ribosylation. In vivo in a mouse model of BRCA1-linked triple-negative breast cancer (K14-Cre BRCA1(f/f)p53(f/f)), the PI3K inhibitor BKM120 led to a precipitous drop in DNA synthesis within 8 h of drug treatment, whereas DNA synthesis in normal tissues was less affected. In this mouse model, combined PI3K and PARP inhibition was superior to either agent alone to induce durable remissions of established tumors.
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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.