ArticleSignal transduction and targeted therapy2020
A CRISPR knockout negative screen reveals synergy between CDKs inhibitor and metformin in the treatment of human cancer in vitro and in vivo.
Article in Signal transduction and targeted therapy, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
12 citing papers in PubMed, 21 citations in OpenAlex.
- Letrozole, abemaciclib and metformin in endometrial cancer: a non-randomized phase 2 trial.Nature communications · 2025Trial
- A transcriptional biosensor reveals mechanisms of α-ketoglutarate signaling to chromatin.Science (New York, N.Y.) · 2026Article
- Glucose restriction reprograms lipid metabolism and enhances immunotherapy through ZNRF3-Wnt-SCD signaling axis.Journal for immunotherapy of cancer · 2026Article
- mTOR-driven autophagy suppression defines metabolic vulnerability in CDK4/6 inhibitor-resistant HRCell death & disease · 2026Article
- Metformin Sensitizes HR+/HER2- Breast Cancer Cells to CDK4/6 Inhibitor via Suppressing of PI3K/AKT/mTOR Signaling Pathway.Drug design, development and therapy · 2026Article
- Nickel Nanoparticles Promote Lung Adenocarcinoma Progression via CDK1-Mediated Fatty Acid Metabolism Regulation.International journal of molecular sciences · 2025Article
- GDF15 negatively regulates chemosensitivity via TGFBR2-AKT pathway-dependent metabolism in esophageal squamous cell carcinoma.Frontiers of medicine · 2023Article
- Gilteritinib Enhances Anti-Tumor Efficacy of CDK4/6 Inhibitor, Abemaciclib in Lung Cancer Cells.Frontiers in pharmacology · 2022Article
- AHR mediates the aflatoxin B1 toxicity associated with hepatocellular carcinoma.Signal transduction and targeted therapy · 2021Article
- Review
- Article
- Suppressive effects of plumbagin on the growth of human bladder cancer cells via PI3K/AKT/mTOR signaling pathways and EMT.Cancer cell international · 2020Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Laboratory research and pharmacoepidemiology provide support for metformin as a potential antitumor agent. However, the lack of a clear understanding of the indications of metformin limits its efficacy. Here, we performed a genome-wide CRISPR knockout negative screen to identify potential targets that might synergize with metformin. Next-generation sequencing of pooled genomic DNAs isolated from surviving cells after 18 days of metformin treatment (T18) compared to those of the untreated cells at day 0 (T0) yielded candidate genes. Knockdown of a group of cyclin-dependent kinases (CDKs), including CDK1, CDK4, and CDK6, confirmed the results of the screen. Combination treatment of the CDKs inhibitor abemaciclib with metformin profoundly inhibited tumor viability in vitro and in vivo. Although cell cycle parameters were not further altered under the combination treatment, investigation of the metabolome revealed significant changes in cell metabolism, especially with regard to fatty acid oxidation, the tricarboxylic acid cycle and aspartate metabolism. Such changes appeared to be mediated through inhibition of the mTOR pathway. Collectively, our study suggests that the combination of CDKs inhibitor with metformin could be recognized as a potential therapy in future clinical applications.
Indexed as
Identifiers
What OpenQuestion holds
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.