ArticleThe pharmacogenomics journal2019
An exploratory study by DMET array identifies a germline signature associated with imatinib response in gastrointestinal stromal tumor.
Article in The pharmacogenomics journal, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed.
- Exploring nanotechnology solutions for improved outcomes in gastrointestinal stromal tumors.Heliyon · 2024Review
- Thai pharmacogenomics database -2 (TPGxD-2) sequel to TPGxD-1, analyzing genetic variants in 26 non-VIPGx genes within the Thai population.Clinical and translational science · 2024Article
- The GIST of it all: management of gastrointestinal stromal tumors (GIST) from the first steps to tailored therapy. A bibliometric analysis.Langenbeck's archives of surgery · 2024Article
- Validation of single nucleotide polymorphisms potentially related to R-CHOP resistance in diffuse large B-cell lymphoma patients.Cancer drug resistance (Alhambra, Calif.) · 2024Article
- Impact of genetic variants in the solute carrier (Cancer drug resistance (Alhambra, Calif.) · 2024Review
- Molecular Mechanisms of Gastrointestinal Stromal Tumors and Their Impact on Systemic Therapy Decision.Cancers · 2023Review
- CYP2C8*3 and *4 define CYP2C8 phenotype: An approach with the substrate cinitapride.Clinical and translational science · 2022Article
- Current Molecular Profile of Gastrointestinal Stromal Tumors and Systemic Therapeutic Implications.Cancers · 2022Review
- Association between Germline Single-Nucleotide Variants in ADME Genes and Major Molecular Response to Imatinib in Chronic Myeloid Leukemia Patients.Journal of clinical medicine · 2022Article
- Pharmacogenetic Profiling in High-Risk Soft Tissue Sarcomas Treated with Neoadjuvant Chemotherapy.Journal of personalized medicine · 2022Article
- Pharmacogenomics and functional imaging to predict irinotecan pharmacokinetics and pharmacodynamics: the predict IR study.Cancer chemotherapy and pharmacology · 2021Observational
- Bioinformatics-Based Identification of HDAC Inhibitors as Potential Drugs to Target EGFR Wild-Type Non-Small-Cell Lung Cancer.Frontiers in oncology · 2021Article
- Pharmacogenetics for severe adverse drug reactions induced by molecular-targeted therapy.Cancer science · 2020Review
- Pharmacogenomics to Predict Tumor Therapy Response: A Focus on ATP-Binding Cassette Transporters and Cytochromes P450.Journal of personalized medicine · 2020Review
- HIF-1α regulates cellular metabolism, and Imatinib resistance by targeting phosphogluconate dehydrogenase in gastrointestinal stromal tumors.Cell death & disease · 2020Article
- The rs17084733 variant in theEpigenetics · 2019Article
- Somatic pharmacogenomics of gastrointestinal stromal tumor.Cancer drug resistance (Alhambra, Calif.) · 2019Review
- Clinical relevance of circulating molecules in cancer: focus on gastrointestinal stromal tumors.Therapeutic advances in medical oncology · 2019Review
Corrections and comments
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Authors and funding
16 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Imatinib represents the standard therapy for gastrointestinal stromal tumor (GIST) patients with metastatic/unresectable disease. Despite the excellent results achieved with its introduction, the majority of patients quite invariably experience disease progression. The aim of this study was to understand the contribution of germline DNA polymorphisms in discriminating between imatinib clinical response [evaluated as progression free survival (PFS)] and toxicity. In particular, a discovery cohort (34 GIST with a KIT exon 11 primary mutation, and no toxicity) was analyzed through DMET array that interrogates 1936 variants in 231 genes of the ADME process. We further confirmed the genotype of selected variants in an extended cohort of 49 patients (the original cohort and 15 new cases, all with exon 11 primary mutation), identifying 6 SNPs- ABCB4 rs1202283, ABCC2 rs2273697, ABCG1 rs1541290, CYP11B1 rs7003319, CYP7B1 rs6987861, and NQO1 rs10517-significantly associated with response to imatinib. Three SNPs, ABCB4 rs1202283, ABCC2 rs2273697, and NQO1 rs10517, which had a significant association after adjusted multivariate analysis, were included in a genetic prediction model. We confirmed that these SNPs could stratify the cohort of 49 patients according to the risk of developing progression under imatinib treatment. In conclusion, we identified a genetic signature of response to imatinib therapy in GIST patients able to stratify patients at low and high risk to progress, according to their genotype.
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