ArticleCancer letters2022
EZH2 inhibition confers PIK3CA-driven lung tumors enhanced sensitivity to PI3K inhibition.
Article in Cancer letters, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 29 citations in OpenAlex.
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- TRERNA1-mediated acetylation represses ferroptosis of non-small cell lung cancer cells via the KAT6A/H3K23ac/TRIM24-PIK3CA pathway.Human cell · 2026Article
- AC decoction augments chemotherapy in NSCLC by reshaping the tumor immune microenvironment: attenuating Tregs and enhancing CD8Scientific reports · 2026Article
- Targeting signaling pathways in lymphoma: From molecular mechanisms to clinical breakthroughs.Chinese medical journal · 2026Review
- Identification of a neoplastic Tfh-like cellular subset in a mouse model of angioimmunoblastic T cell lymphoma.Frontiers in oncology · 2026Article
- Death-ision: the link between cellular resilience and cancer resistance to treatments.Molecular cancer · 2025Review
- Methionine Restriction Reduces Lung Cancer Progression and Increases Chemotherapy Response.bioRxiv : the preprint server for biology · 2024Article
- Identification of genetic associations between acute myocardial infarction and non-small cell lung cancer.Frontiers in molecular biosciences · 2024Article
- Role and potential therapeutic value of histone methyltransferases in drug resistance mechanisms in lung cancer.Frontiers in oncology · 2024Review
- Mechanisms of resistance to targeted therapy and immunotherapy in non-small cell lung cancer: promising strategies to overcoming challenges.Frontiers in immunology · 2024Review
- CBF-Beta Mitigates PI3K-Alpha-Specific Inhibitor Killing through PIM1 in PIK3CA-Mutant Gastric Cancer.Molecular cancer research : MCR · 2023Article
- Phosphorylation of EZH2 differs HER2-positive breast cancer invasiveness in a site-specific manner.BMC cancer · 2023Article
- Using Artificial Intelligence to Identify Tumor Microenvironment Heterogeneity in Non-Small Cell Lung Cancers.Laboratory investigation; a journal of technical methods and pathology · 2023Article
- Lysine methylation promotes NFAT5 activation and determines temozolomide efficacy in glioblastoma.Nature communications · 2023Article
- Polycomb deficiency drives a FOXP2-high aggressive state targetable by epigenetic inhibitors.Nature communications · 2023Article
- Genome-wide gain-of-function screening identifies EZH2 mediating resistance to PI3Kα inhibitors in oesophageal squamous cell carcinoma.Clinical and translational medicine · 2022Article
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
Members of the PI3K signaling pathway, especially PIK3CA, the gene encoding the catalytic subunit of the PI3K complex, are highly mutated and amplified in various cancer types, including non-small cell lung cancer. Although PI3K inhibitors have been used in clinics for follicular lymphoma and chronic lymphocytic leukemia, no agents targeting PI3K aberrations in lung cancer have been approved by the FDA so far. In this study, we observed that PIK3CA-E545K, the most common mutation in lung cancer, harbored a modest induction of stem-like properties in lung epithelial cells, and drove development of adenocarcinoma autochthonously when paired with p53 loss in a murine mouse model. We also found that PIK3CA-mutant of amplified lung cancer cells were sensitive to EZH2 inhibition. EZH2 inhibition synergized with PI3K inhibition in human cancer cells in vitro and worked together efficiently in vivo. Mechanistically, EZH2 inhibition cooperated with PI3K inhibition to produce a more potent suppression of phospho-AKT downstream of PI3K. This study suggests a promising combination therapy to combat lung cancers with PIK3CA mutation or amplification. Both copanlisib, the PI3K inhibitor, and tazemetostat, the EZH2 inhibitor, are FDA-approved, which should enhance the clinical translation of this work.
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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.