ArticleClinical cancer research : an official journal of the American Association for Cancer Research2021
Global Phosphoproteomics Reveal CDK Suppression as a Vulnerability to KRas Addiction in Pancreatic Cancer.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 34 citations in OpenAlex.
- Integrative proteomic characterization of human lung adenocarcinoma with KRAS G12 mutations reveals molecular pathogenesis.Journal of advanced research · 2026Article
- The Emerging Role of Transcription-Associated Cyclin-Dependent Kinases in Gastrointestinal Tumors.Cancers · 2026Review
- Recent advances in phosphoproteomics based on mass spectrometry and its clinical application prospects.Frontiers in pharmacology · 2026Review
- Post-Translational Modifications: Key "Regulators" of Pancreatic Cancer Malignant Phenotype-Advances in Mechanisms and Targeted Therapies.Biomedicines · 2025Review
- Phosphorylation of USP33 by CDK1 stabilizes the mTORC2 component SIN1.Cell death & disease · 2025Article
- Transforming cancer treatment: integrating patient-derived organoids and CRISPR screening for precision medicine.Frontiers in pharmacology · 2025Review
- Mechanisms of Berberine in anti-pancreatic ductal adenocarcinoma revealed by integrated multi-omics profiling.Scientific reports · 2024Article
- Omics-based molecular classifications empowering in precision oncology.Cellular oncology (Dordrecht, Netherlands) · 2024Review
- Design, synthesis and biological evaluation of 2-((4-sulfamoylphenyl)amino)-pyrrolo[2,3-d]pyrimidine derivatives as CDK inhibitors.Journal of enzyme inhibition and medicinal chemistry · 2023Article
- Inhibition of CDK1 Overcomes Oxaliplatin Resistance by Regulating ACSL4-mediated Ferroptosis in Colorectal Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
- Functional and Clinical Proteomic Exploration of Pancreatic Cancer.Molecular & cellular proteomics : MCP · 2023Review
- Principles of phosphoproteomics and applications in cancer research.The Biochemical journal · 2023Article
- Mutant K-Ras in Pancreatic Cancer: An Insight on the Role of Wild-Type N-Ras and K-Ras-Dependent Cell Cycle Regulation.Current issues in molecular biology · 2023Article
- Novel mutant KRAS addiction signature predicts response to the combination of ERBB and MEK inhibitors in lung and pancreatic cancers.iScience · 2023Article
- Mitochondria-Related Transcriptome Characterization Associated with the Immune Microenvironment, Therapeutic Response and Survival Prediction in Pancreatic Cancer.International journal of molecular sciences · 2023Article
- The CDK inhibitor AT7519 inhibits human glioblastoma cell growth by inducing apoptosis, pyroptosis and cell cycle arrest.Cell death & disease · 2023Article
- Review
- A review on the role of cyclin dependent kinases in cancers.Cancer cell international · 2022Review
- Inhibitory Response to CK II Inhibitor Silmitasertib and CDKs Inhibitor Dinaciclib Is Related to Genetic Differences in Pancreatic Ductal Adenocarcinoma Cell Lines.International journal of molecular sciences · 2022Article
- Network controllability solutions for computational drug repurposing using genetic algorithms.Scientific reports · 2022Article
Corrections and comments
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Authors and funding
16 authors at 3 institutions in 1 country.
Funding
Abstract
purposeAmong human cancers that harbor mutant (mt) KRas, some, but not all, are dependent on mt KRas. However, little is known about what drives KRas dependency. EXPERIMENTAL
designGlobal phosphoproteomics, screening of a chemical library of FDA drugs, and genome-wide CRISPR/Cas9 viability database analysis were used to identify vulnerabilities of KRas dependency.
resultsGlobal phosphoproteomics revealed that KRas dependency is driven by a cyclin-dependent kinase (CDK) network. CRISPR/Cas9 viability database analysis revealed that, in mt KRas-driven pancreatic cancer cells, knocking out the cell-cycle regulators CDK1 or CDK2 or the transcriptional regulators CDK7 or CDK9 was as effective as knocking out KRas. Furthermore, screening of a library of FDA drugs identified AT7519, a CDK1, 2, 7, and 9 inhibitor, as a potent inducer of apoptosis in mt KRas-dependent, but not in mt KRas-independent, human cancer cells.
conclusionsA link between CDK hyperactivation and mt KRas dependency was uncovered and pharmacologically exploited to abrogate mt KRas-driven pancreatic cancer in highly relevant models, warranting clinical investigations of AT7519 in patients with pancreatic cancer.
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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.