ArticleCell2009
A genome-wide RNAi screen identifies multiple synthetic lethal interactions with the Ras oncogene.
Article in Cell, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT06736717 (A Phase 1b/2 Trial of Onvansertib in Combination With NALIRIFOX for First Line Treatment of Advanced Pancreatic Cancer), which is not on this map. Cited by 622 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.
A Phase 1b/2 Trial of Onvansertib in Combination With NALIRIFOX for First Line Treatment of Advanced Pancreatic Cancer
Who cites it
622 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Synthetic lethal gene pairs: Experimental approaches and predictive models.Frontiers in genetics · 2022Pooled it
- Onvansertib in Combination With Chemotherapy and Bevacizumab in Second-Line Treatment ofJournal of clinical oncology : official journal of the American Society of Clinical Oncology · 2025Trial
- Exceptional responders with invasive mucinous adenocarcinomas: a phase 2 trial of bortezomib in patients withCold Spring Harbor molecular case studies · 2019Trial
- Synthetic lethality in cancer: mechanisms, therapeutic exploitation and clinical translation.Signal transduction and targeted therapy · 2026Review
- Changes in the transcriptome and synthetic lethal dependencies followingProceedings of the National Academy of Sciences of the United States of America · 2026Article
- Coordinated Immune Activation Following KRAS Inhibition in Syngeneic Models Reveals Molecular Pathways that Potentiate and Limit Antitumor Immunity.Cancer immunology research · 2026Article
- XRCC1 deficiency drives telomeric chromatin leakage, inflammatory signalling and senescence.Redox biology · 2026Article
- An ALKBH3 Inhibitor HUHS199 Suppresses Proliferation of Glioblastoma Cells by Targeting 1-Methyladenosine on GADD45A mRNA.Chemical biology & drug design · 2026Article
- 3'UTR-directed, kinase-proximal mRNA decay inhibits C/EBPβ phosphorylation/activation to suppress senescence in tumor cells.iScience · 2026Article
- Corilagin induces apoptosis in glioblastoma cells by disrupting metabolic homeostasis: a metabolomics perspective.Die Naturwissenschaften · 2026Article
- Cyclin C promotes pancreatic developmentand suppresses cancer initiation by maintenance of the autophagy-lysosome pathway.iScience · 2026Article
- MVGAE: A Multi-View Graph Auto-Encoder Model for Drug Prediction of Non-Small Cell Lung Cancer Based on Synthetic Lethality.Current issues in molecular biology · 2026Article
- Human DEAH-box helicase 8 regulates HSF1-mediated stress response and cancer-associated pre-mRNA splicing in tumour cells.NAR cancer · 2026Article
- Targeting a Glutamic Acid in PDEδ with Fluoromethyl-Aryl Electrophiles Impairs K-Ras Signaling.Journal of medicinal chemistry · 2026Article
- KRAS-Driven Hypertranscription and Metastatic Dissemination in Colorectal Cancer Could be Overcome by Targeting the NMHC IIA/ PLK1 Signaling Axis with a Novel Acridine Derivative.International journal of biological sciences · 2026Article
- Synthetic lethality in cancer drug discovery: challenges and opportunities.Nature reviews. Drug discovery · 2026Review
- Article
- The function of MYC in base excision repair protects against RAS-induced senescence.Nucleic acids research · 2025Article
- Differential Response and Resistance to KRAS-Targeted Therapy.Molecular carcinogenesis · 2025Review
- PLK1 inhibitors for the treatment of colorectal cancer.Annals of medicine and surgery (2012) · 2025Review
562 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on by
- Commented on by
Authors and funding
8 authors.
Funding
Abstract
Oncogenic mutations in the small GTPase Ras are highly prevalent in cancer, but an understanding of the vulnerabilities of these cancers is lacking. We undertook a genome-wide RNAi screen to identify synthetic lethal interactions with the KRAS oncogene. We discovered a diverse set of proteins whose depletion selectively impaired the viability of Ras mutant cells. Among these we observed a strong enrichment for genes with mitotic functions. We describe a pathway involving the mitotic kinase PLK1, the anaphase-promoting complex/cyclosome, and the proteasome that, when inhibited, results in prometaphase accumulation and the subsequent death of Ras mutant cells. Gene expression analysis indicates that reduced expression of genes in this pathway correlates with increased survival of patients bearing tumors with a Ras transcriptional signature. Our results suggest a previously underappreciated role for Ras in mitotic progression and demonstrate a pharmacologically tractable pathway for the potential treatment of cancers harboring Ras mutations.
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.