ArticleCancer cell2008
Discovery of drug-resistant and drug-sensitizing mutations in the oncogenic PI3K isoform p110 alpha.
Article in Cancer cell, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
53 citing papers in PubMed, 96 citations in OpenAlex.
- Contemporary design of small-molecule kinase modulators: orthosteric, allosteric and induced-proximity strategies.Nature reviews. Drug discovery · 2026Review
- Systematic evaluation of computational tools to predict the effects of mutations on protein-ligand binding affinity in the absence of experimental structures.Briefings in bioinformatics · 2026Article
- Article
- MYC is a clinically significant driver of mTOR inhibitor resistance in breast cancer.The Journal of experimental medicine · 2023Article
- Functional impact and molecular binding modes of drugs that target the PI3K isoform p110δ.Communications biology · 2023Article
- ExploringMicrobial cell (Graz, Austria) · 2021Review
- DGAT1 Expression Promotes Ovarian Cancer Progression and Is Associated with Poor Prognosis.Journal of immunology research · 2021Article
- Monitoring Phosphoinositide Fluxes and Effectors During Leukocyte Chemotaxis and Phagocytosis.Frontiers in cell and developmental biology · 2021Review
- Phosphoinositide 3-Kinase Signaling in the Tumor Microenvironment: What Do We Need to Consider When Treating Chronic Lymphocytic Leukemia With PI3K Inhibitors?Frontiers in immunology · 2020Review
- Defining the landscape of ATP-competitive inhibitor resistance residues in protein kinases.Nature structural & molecular biology · 2020Article
- Dissecting mechanisms of resistance to targeted drug combination therapy in human colorectal cancer.Oncogene · 2019Article
- The mechanism of PI3Kα activation at the atomic level.Chemical science · 2019Article
- Biomarkers of Everolimus Sensitivity in Hormone Receptor-Positive Breast Cancer.Journal of breast cancer · 2017Review
- Targeting the Phosphatidylinositol-3-kinase Pathway in Gastric Cancer: Can Omics Improve Outcomes?International neurourology journal · 2016Review
- BKM-120 (Buparlisib): A Phosphatidyl-Inositol-3 Kinase Inhibitor with Anti-Invasive Properties in Glioblastoma.Scientific reports · 2016Article
- A novel approach to the discovery of anti-tumor pharmaceuticals: searching for activators of liponecrosis.Oncotarget · 2016Review
- Cell type-specific abundance of 4EBP1 primes prostate cancer sensitivity or resistance to PI3K pathway inhibitors.Science signaling · 2015Article
- p110α Hot Spot Mutations E545K and H1047R Exert Metabolic Reprogramming Independently of p110α Kinase Activity.Molecular and cellular biology · 2015Article
- Discovery of a Potent Class of PI3Kα Inhibitors with Unique Binding Mode via Encoded Library Technology (ELT).ACS medicinal chemistry letters · 2015Article
- Identification of a Non-Gatekeeper Hot Spot for Drug-Resistant Mutations in mTOR Kinase.Cell reports · 2015Article
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
p110 alpha (PIK3CA) is the most frequently mutated kinase in human cancer, and numerous drugs targeting this kinase are currently in preclinical development or early-stage clinical trials. Clinical resistance to protein kinase inhibitors frequently results from point mutations that block drug binding; similar mutations in p110 alpha are likely, but currently none have been reported. Using a S. cerevisiae screen against a structurally diverse panel of PI3K inhibitors, we have identified a potential hotspot for resistance mutations (I800), a drug-sensitizing mutation (L814C), and a surprising lack of resistance mutations at the "gatekeeper" residue. Our analysis further reveals that clinical resistance to these drugs may be attenuated by using multitargeted inhibitors that simultaneously inhibit additional PI3K pathway members.
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Registered trials
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.