ArticleNeoplasia (New York, N.Y.)2013
Synthetic lethality screen identifies RPS6KA2 as modifier of epidermal growth factor receptor activity in pancreatic cancer.
Article in Neoplasia (New York, N.Y.), 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 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
22 citing papers in PubMed, 39 citations in OpenAlex.
- Investigating the Mechanism of Astragalus mongholicus-Mediated Treatment of Silicosis in Mice from the Perspective of Alternative Splicing.Current drug targets · 2026Article
- miR-512-3p/RPS6KA2 Axis Regulates Cisplatin Resistance in Ovarian Cancer via Autophagy and Ferroptosis.Oncology research · 2025Article
- Integrating machine learning and single-cell sequencing to identify shared biomarkers in type 1 diabetes mellitus and clear cell renal cell carcinoma.Frontiers in oncology · 2025Article
- RSK3 switches cell fate: from stress-induced senescence to malignant progression.Journal of experimental & clinical cancer research : CR · 2023Article
- BI-D1870 Induces Mitotic Dysfunction and Apoptosis in Neuroblastoma by Regulating the PI3K-Akt-mTORC1 Signal Axis.Cancers · 2023Article
- DNA Methylation as a Diagnostic, Prognostic, and Predictive Biomarker in Head and Neck Cancer.International journal of molecular sciences · 2023Review
- Establishment of a new prognostic risk model of MAPK pathway-related molecules in kidney renal clear cell carcinoma based on genomes and transcriptomes analysis.Frontiers in oncology · 2023Article
- ncRNAs mediated RPS6KA2 inhibits ovarian cancer proliferation via p38/MAPK signaling pathway.Frontiers in oncology · 2023Article
- Article
- Exploration of an Integrative Prognostic Model of Radiogenomics Features With Underlying Gene Expression Patterns in Clear Cell Renal Cell Carcinoma.Frontiers in oncology · 2021Article
- Genome-wide association study of café-au-lait macule number in neurofibromatosis type 1.Molecular genetics & genomic medicine · 2020Article
- Phenotypic screening using large-scale genomic libraries to identify drug targets for the treatment of cancer.Oncology letters · 2020Review
- Identification of a transcriptomic signature with excellent survival prediction for squamous cell carcinoma of the cervix.American journal of cancer research · 2020Article
- Human Papillomavirus 11 Early Protein E6 Activates Autophagy by Repressing AKT/mTOR and Erk/mTOR.Journal of virology · 2019Article
- APIM-peptide targeting PCNA improves the efficacy of docetaxel treatment in the TRAMP mouse model of prostate cancer.Oncotarget · 2018Article
- Ribosomal proteins: insight into molecular roles and functions in hepatocellular carcinoma.Oncogene · 2018Review
- MptpB Promotes Mycobacteria Survival by Inhibiting the Expression of Inflammatory Mediators and Cell Apoptosis in Macrophages.Frontiers in cellular and infection microbiology · 2018Article
- Systematic screening of isogenic cancer cells identifies DUSP6 as context-specific synthetic lethal target in melanoma.Oncotarget · 2017Article
- Cellular and molecular aspects of pancreatic cancer.Acta histochemica · 2016Review
- The kinome 'at large' in cancer.Nature reviews. Cancer · 2016Review
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 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Pancreatic cancer is characterized by a high degree of resistance to chemotherapy. Epidermal growth factor receptor (EGFR) inhibition using the small-molecule inhibitor erlotinib was shown to provide a small survival benefit in a subgroup of patients. To identify kinases whose inhibition acts synergistically with erlotinib, we employed a kinome-wide small-interfering RNA (siRNA)-based loss-of-function screen in the presence of erlotinib. Of 779 tested kinases, we identified several targets whose inhibition acted synergistically lethal with EGFR inhibition by erlotinib, among them the S6 kinase ribosomal protein S6 kinase 2 (RPS6KA2)/ribosomal S6 kinase 3. Activated RPS6KA2 was expressed in approximately 40% of 123 human pancreatic cancer tissues. RPS6KA2 was shown to act downstream of EGFR/RAS/mitogen-activated protein kinase kinase (MEK)/extracellular-signal regulated kinase (ERK) signaling and was activated by EGF independently of the presence of KRAS mutations. Knockdown of RPS6KA2 by siRNA led to increased apoptosis only in the presence of erlotinib, whereas RPS6KA2 activation or overexpression rescued from erlotinib- and gemcitabine-induced apoptosis. This effect was at least in part mediated by downstream activation of ribosomal protein S6. Genetic as well as pharmacological inhibition of RPS6KA2 by the inhibitor BI-D1870 acted synergistically with erlotinib. By applying this synergistic lethality screen using a kinome-wide RNA interference-library approach, we identified RPS6KA2 as potential drug target whose inhibition synergistically enhanced the effect of erlotinib on tumor cell survival. This kinase therefore represents a promising drug candidate suitable for the development of novel inhibitors for pancreatic cancer therapy.
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.