ArticlePloS one2012
KRAS mutation is a predictor of oxaliplatin sensitivity in colon cancer cells.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers, 1 of them a synthesis that pooled it.
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Who cites it
26 citing papers in PubMed, 1 synthesis or guideline pooled it, 48 citations in OpenAlex.
- Genetic Variants in DNA Repair Pathways as Potential Biomarkers in Predicting Treatment Outcome of Intraperitoneal Chemotherapy in Patients With Colorectal Peritoneal Metastasis: A Systematic Review.Frontiers in pharmacology · 2020Pooled it
- KRAS codon 12 and 13 mutations in relation to disease-free survival in BRAF-wild-type stage III colon cancers from an adjuvant chemotherapy trial (N0147 alliance).Clinical cancer research : an official journal of the American Association for Cancer Research · 2014Trial
- Article
- Article
- Oxidative Phosphorylation as a Predictive Biomarker of Oxaliplatin Response in Colorectal Cancer.Biomolecules · 2024Article
- CRISPR/Cas9-mediated silencing of CD44: unveiling the role of hyaluronic acid-mediated interactions in cancer drug resistance.Naunyn-Schmiedeberg's archives of pharmacology · 2024Review
- Carcinoid Syndrome: Preclinical Models and Future Therapeutic Strategies.International journal of molecular sciences · 2023Review
- Article
- Prognostic Value ofCancers · 2022Article
- The human AP-endonuclease 1 (APE1) is a DNA G-quadruplex structure binding protein and regulates KRAS expression in pancreatic ductal adenocarcinoma cells.Nucleic acids research · 2022Article
- Validation of Genetic Markers Associated with Survival in Colorectal Cancer Patients Treated with Oxaliplatin-Based Chemotherapy.Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology · 2022Observational
- oncoPredict: an R package for predicting in vivo or cancer patient drug response and biomarkers from cell line screening data.Briefings in bioinformatics · 2021Article
- Article
- Phenoxodiol sensitizes metastatic colorectal cancer cells to 5-fluorouracil- and oxaliplatin-induced apoptosis through intrinsic pathway.EXCLI journal · 2020Article
- Sensitization of colorectal cancer to irinotecan therapy by PARP inhibitor rucaparib.Investigational new drugs · 2019Article
- In Vitro and in Vivo antitumor activity and the mechanism of siphonodictyal B in human colon cancer cells.Cancer medicine · 2019Article
- WBSCR22 confers oxaliplatin resistance in human colorectal cancer.Scientific reports · 2017Article
- Lipoprotein-biomimetic nanostructure enables efficient targeting delivery of siRNA to Ras-activated glioblastoma cells via macropinocytosis.Nature communications · 2017Article
- Long-lasting reduction in clonogenic potential of colorectal cancer cells by sequential treatments with 5-azanucleosides and topoisomerase inhibitors.BMC cancer · 2016Article
- Distinct gene expression profiles of proximal and distal colorectal cancer: implications for cytotoxic and targeted therapy.The pharmacogenomics journal · 2015Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Molecular biomarkers to determine the effectiveness of targeted therapies in cancer treatment have been widely adopted in colorectal cancer (CRC), but those to predict chemotherapy sensitivity remain poorly defined. We tested our hypothesis that KRAS mutation may be a predictor of oxaliplatin sensitivity in CRC. KRAS was knocked-down in KRAS-mutant CRC cells (DLD-1(G13D) and SW480(G12V)) by small interfering RNAs (siRNA) and overexpressed in KRAS-wild-type CRC cells (COLO320DM) by KRAS-mutant vectors to generate paired CRC cells. These paired CRC cells were tested by oxaliplatin, irinotecan and 5FU to determine the change in drug sensitivity by MTT assay and flow cytometry. Reasons for sensitivity alteration were further determined by western blot and real-time quantitative reverse transcriptase polymerase chain reaction (qRT -PCR). In KRAS-wild-type CRC cells (COLO320DM), KRAS overexpression by mutant vectors caused excision repair cross-complementation group 1 (ERCC1) downregulation in protein and mRNA levels, and enhanced oxaliplatin sensitivity. In contrast, in KRAS-mutant CRC cells (DLD-1(G13D) and SW480(G12V)), KRAS knocked-down by KRAS-siRNA led to ERCC1 upregulation and increased oxaliplatin resistance. The sensitivity of irinotecan and 5FU had not changed in the paired CRC cells. To validate ERCC1 as a predictor of sensitivity for oxaliplatin, ERCC1 was knocked-down by siRNA in KRAS-wild-type CRC cells, which restored oxaliplatin sensitivity. In contrast, ERCC1 was overexpressed by ERCC1-expressing vectors in KRAS-mutant CRC cells, and caused oxaliplatin resistance. Overall, our findings suggest that KRAS mutation is a predictor of oxaliplatin sensitivity in colon cancer cells by the mechanism of ERCC1 downregulation.
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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.