ArticleBMC medical genomics2010
A gene expression signature of RAS pathway dependence predicts response to PI3K and RAS pathway inhibitors and expands the population of RAS pathway activated tumors.
Article in BMC medical genomics, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 87 papers.
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87 citing papers in PubMed, 152 citations in OpenAlex.
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- Combination of the mTOR inhibitor ridaforolimus and the anti-IGF1R monoclonal antibody dalotuzumab: preclinical characterization and phase I clinical trial.Clinical cancer research : an official journal of the American Association for Cancer Research · 2015Trial
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- Effect of simvastatin plus cetuximab/irinotecan for KRAS mutant colorectal cancer and predictive value of the RAS signature for treatment response to cetuximab.Investigational new drugs · 2014Trial
- Comprehensive biomarker analysis and final efficacy results of sorafenib in the BATTLE trial.Clinical cancer research : an official journal of the American Association for Cancer Research · 2013Trial
- Development of an APC and TP53-based duplex sequencing assay to positively predict colorectal cancer response to anti-EGFR therapy.Cellular oncology (Dordrecht, Netherlands) · 2026Article
- Advanced dual primary male breast cancer and lung cancer: A case report and literature review.Oncology letters · 2026Article
- Wild-type KRAS activation drives evasion of interferon-mediated immunity and resistance to immunotherapy in hepatocellular carcinoma.Nature communications · 2025Article
- Conception and Concern: A Review of Breast Cancer Risk in Assisted Reproductive Technology.International journal of biological sciences · 2025Review
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- Identification of genes predicting chemoresistance and short survival in ovarian cancer.Translational cancer research · 2024Article
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- Tumor Cell Resistance to the Inhibition of BRAF and MEK1/2.International journal of molecular sciences · 2023Review
- Direct GDP-KRASTherapeutic advances in medical oncology · 2023Review
- The relationships of OSBPL3 expression with KI-67 expression and KRAS mutations in CRC: implications for diagnosis and prognosis.BMC medical genomics · 2022Article
- Hyper-active RAS/MAPK introduces cancer-specific mitotic vulnerabilities.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- RAS oncogenic activity predicts response to chemotherapy and outcome in lung adenocarcinoma.Nature communications · 2022Article
- Dynamic and adaptive cancer stem cell population admixture in colorectal neoplasia.Cell stem cell · 2022Article
- Transcriptomic Determinants of Response to Pembrolizumab Monotherapy across Solid Tumor Types.Clinical cancer research : an official journal of the American Association for Cancer Research · 2022Article
27 more citing papers are in PubMed but not listed here.
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Authors and funding
18 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundHyperactivation of the Ras signaling pathway is a driver of many cancers, and RAS pathway activation can predict response to targeted therapies. Therefore, optimal methods for measuring Ras pathway activation are critical. The main focus of our work was to develop a gene expression signature that is predictive of RAS pathway dependence.
methodsWe used the coherent expression of RAS pathway-related genes across multiple datasets to derive a RAS pathway gene expression signature and generate RAS pathway activation scores in pre-clinical cancer models and human tumors. We then related this signature to KRAS mutation status and drug response data in pre-clinical and clinical datasets.
resultsThe RAS signature score is predictive of KRAS mutation status in lung tumors and cell lines with high (> 90%) sensitivity but relatively low (50%) specificity due to samples that have apparent RAS pathway activation in the absence of a KRAS mutation. In lung and breast cancer cell line panels, the RAS pathway signature score correlates with pMEK and pERK expression, and predicts resistance to AKT inhibition and sensitivity to MEK inhibition within both KRAS mutant and KRAS wild-type groups. The RAS pathway signature is upregulated in breast cancer cell lines that have acquired resistance to AKT inhibition, and is downregulated by inhibition of MEK. In lung cancer cell lines knockdown of KRAS using siRNA demonstrates that the RAS pathway signature is a better measure of dependence on RAS compared to KRAS mutation status. In human tumors, the RAS pathway signature is elevated in ER negative breast tumors and lung adenocarcinomas, and predicts resistance to cetuximab in metastatic colorectal cancer.
conclusionsThese data demonstrate that the RAS pathway signature is superior to KRAS mutation status for the prediction of dependence on RAS signaling, can predict response to PI3K and RAS pathway inhibitors, and is likely to have the most clinical utility in lung and breast tumors.
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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.