ArticleCancer biology & medicine2019
Simultaneous inhibition of PI3Kα and CDK4/6 synergistically suppresses KRAS-mutated non-small cell lung cancer.
Article in Cancer biology & medicine, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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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.
The trial behind it
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Who cites it
17 citing papers in PubMed, 40 citations in OpenAlex.
- Applications of pyroptosis activators in tumor immunotherapy.Materials today. Bio · 2024Review
- Molecular Targeting of the Phosphoinositide-3-Protein Kinase (PI3K) Pathway across Various Cancers.International journal of molecular sciences · 2024Review
- CDK4/6 inhibitors in lung cancer: current practice and future directions.European respiratory review : an official journal of the European Respiratory Society · 2024Review
- Intact regulation of G1/S transition renders esophageal squamous cell carcinoma sensitive to PI3Kα inhibitors.Signal transduction and targeted therapy · 2023Article
- Antitumor pharmacological research in the era of personalized medicine.Acta pharmacologica Sinica · 2022Review
- First-in-human phase Ia study of the PI3Kα inhibitor CYH33 in patients with solid tumors.Nature communications · 2022Article
- Characterization ofJTO clinical and research reports · 2022Article
- Engineering prodrug nanomicelles as pyroptosis inducer for codelivery of PI3K/mTOR and CDK inhibitors to enhance antitumor immunity.Acta pharmaceutica Sinica. B · 2022Article
- Genome-wide gain-of-function screening identifies EZH2 mediating resistance to PI3Kα inhibitors in oesophageal squamous cell carcinoma.Clinical and translational medicine · 2022Article
- Palbociclib Enhances Migration and Invasion of Cancer Cells via Senescence-Associated Secretory Phenotype-Related CCL5 in Non-Small-Cell Lung Cancer.Journal of oncology · 2022Article
- PI3Kα inhibitor CYH33 triggers antitumor immunity in murine breast cancer by activating CD8Journal for immunotherapy of cancer · 2021Article
- mTOR Activity and Autophagy in Senescent Cells, a Complex Partnership.International journal of molecular sciences · 2021Review
- Adaptive resistance to PI3Kα-selective inhibitor CYH33 is mediated by genomic and transcriptomic alterations in ESCC cells.Cell death & disease · 2021Article
- Mechanisms and Implications of CDK4/6 Inhibitors for the Treatment of NSCLC.Frontiers in oncology · 2021Review
- EVI5 is an oncogene that regulates the proliferation and metastasis of NSCLC cells.Journal of experimental & clinical cancer research : CR · 2020Article
- Erratum to Simultaneous inhibition of PI3Kα and CDK4/6 synergistically suppresses KRAS-mutated non-small cell lung cancer.Cancer biology & medicine · 2019Article
- Unbiased screening reveals that blocking exportin 1 overcomes resistance to PI3Kα inhibition in breast cancer.Signal transduction and targeted therapyArticle
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectiveActivating
methodsCell proliferation was detected by sulforhodamine B assay. Cell cycle distribution and apoptosis were measured by flow cytometry. Cell signaling was assessed by Western blot and immunohistochemistry. RNA interference was used to down-regulate the expression of cyclin D1. Human NSCLC xenografts were employed to detect therapeutic efficacy
resultsCYH33 possessed variable activity against a panel of KRAS-mutated NSCLC cell lines. Although CYH33 blocked AKT phosphorylation in all tested cells, Rb phosphorylation decreased in CYH33-sensitive, but not in CYH33-resistant cells, which was consistent with G1 phase arrest in sensitive cells. Combined treatment with the CDK4/6 inhibitor, PD0332991, and CYH33 displayed synergistic activity against the proliferation of both CYH33-sensitive and CYH33-resistant cells, which was accompanied by enhanced G1-phase arrest. Moreover, down-regulation of cyclin D1 sensitized NSCLC cells to CYH33. Reciprocally, CYH33 abrogated the PD0332991-induced up-regulation of cyclin D1 and phosphorylation of AKT in A549 cells. Co-treatment with these two drugs demonstrated synergistic activity against A549 and H23 xenografts, with enhanced inhibition of Rb phosphorylation.
conclusionsSimultaneous inhibition of PI3Kα and CDK4/6 displayed synergistic activity against KRAS-mutated NSCLC. These data provide a mechanistic rationale for the combination of a PI3Kα inhibitor and a CDK4/6 inhibitor for the treatment of KRAS-mutated NSCLC.
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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.