ArticleEMBO molecular medicine2021
Synergistic effects of FGFR1 and PLK1 inhibitors target a metabolic liability in KRAS-mutant cancer.
Article in EMBO molecular medicine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers, 1 of them a synthesis that pooled it.
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
18 citing papers in PubMed, 1 synthesis or guideline pooled it, 22 citations in OpenAlex.
- Nanoparticles Bounded to Interfering RNAs as a Therapy for Pancreatic Cancer: A Systematic Review.Wiley interdisciplinary reviews. Nanomedicine and nanobiotechnologyPooled it
- FGFR signaling and apoptotic regulation in cancer: links to immune evasion, therapeutic resistance, and treatment re-engagement.Frontiers in immunology · 2026Review
- FGFR Aberrations in Solid Tumors: Mechanistic Insights and Clinical Translation of Targeted Therapies.Cancers · 2025Review
- Suppressing the OTUD7A/KDM5B/GABPA axis enhances the sensitivity of cisplatin through inducing ferroptosis in KRAS-mutant LUAD.Cell death & disease · 2025Article
- Lactate dehydrogenase B noncanonically promotes ferroptosis defense in KRAS-driven lung cancer.Cell death and differentiation · 2025Article
- LDHB silencing enhances the effects of radiotherapy by impairing nucleotide metabolism and promoting persistent DNA damage.Scientific reports · 2025Article
- Differentially expressed and alternately spliced genes as a novel tool for genotoxicity: a computerized study in ATT-myc transgenic mice for the recognition of genotoxic and non-genotoxic chemical.Frontiers in genetics · 2025Article
- Clinical relevance of PLK1 in epithelial ovarian cancer.Frontiers in pharmacology · 2025Review
- Onvansertib inhibits cell proliferation and increases sensitivity to paclitaxel in uterine serous cancer cells.American journal of cancer research · 2025Article
- Targeting RAF dimers in RAS mutant tumors: From biology to clinic.Acta pharmaceutica Sinica. B · 2024Review
- Phosphorylation of AHR by PLK1 promotes metastasis of LUAD via DIO2-TH signaling.PLoS genetics · 2023Article
- Review
- Inhibition of Polo-like Kinase 1 by HMN-214 Blocks Cell Cycle Progression and Inhibits Neuroblastoma Growth.Pharmaceuticals (Basel, Switzerland) · 2022Article
- Metabolic synthetic lethality by targeting NOP56 and mTOR in KRAS-mutant lung cancer.Journal of experimental & clinical cancer research : CR · 2022Article
- A Breakthrough Brought about by Targeting KRASCancers · 2022Review
- Primary Hepatoid Adenocarcinoma of the Lung: A Systematic Literature Review.OncoTargets and therapy · 2022Article
- Non-genetic adaptive resistance to KRASFrontiers in oncology · 2022Review
- Synergistic effects of FGFR1 and PLK1 inhibitors target a metabolic liability in KRAS-mutant cancer.EMBO molecular medicine · 2021Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
17 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
KRAS oncoprotein is commonly mutated in human cancer, but effective therapies specifically targeting KRAS-driven tumors remain elusive. Here, we show that combined treatment with fibroblast growth factor receptor 1 (FGFR1) and polo-like kinase 1 (PLK1) inhibitors evoke synergistic cytotoxicity in KRAS-mutant tumor models in vitro and in vivo. Pharmacological and genetic suppression of FGFR1 and PLK1 synergizes to enhance anti-proliferative effects and cell death in KRAS-mutant lung and pancreatic but not colon nor KRAS wild-type cancer cells. Mechanistically, co-targeting FGFR1 and PLK1 upregulates reactive oxygen species (ROS), leading to oxidative stress-activated c-Jun N-terminal kinase (JNK)/p38 pathway and E2F1-induced apoptosis. We further delineate that autophagy protects from PLK1/FGFR1 inhibitor cytotoxicity and that antagonizing the compensation mechanism by clinically approved chloroquine fully realizes the therapeutic potential of PLK1 and FGFR1 targeting therapy, producing potent and durable responses in KRAS-mutant patient-derived xenografts and a genetically engineered mouse model of Kras-induced lung adenocarcinoma. These results suggest a previously unappreciated role for FGFR1 and PLK1 in the surveillance of metabolic stress and demonstrate a synergistic drug combination for treating KRAS-mutant cancer.
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.