HOMEPRODUCTSCOMPANYCONTACTFAQResearchDictionaryPharmaSign Up FREE or Login

Genetic polymorphisms as predictive biomarker of survival in patients with gastrointestinal stromal tumors treated with sunitinib.

Abstract
This study aimed to identify single-nucleotide polymorphisms (SNPs) that are associated with outcome to treatment with sunitinib in patients with advanced gastrointestinal stromal tumors (GIST). Forty-nine SNPS involved in the pharmacokinetic and pharmacodynamic pathway of sunitinib were associated with progression-free survival (PFS) and overall survival (OS) in 127 patients with advanced GIST who have been treated with sunitinib. PFS was significantly longer in carriers of the TT genotype in POR rs1056878 (hazards ratio (HR) 4.310, 95% confidence interval (CI):1.457-12.746, P=0.008). The presence of the T-allele in SLCO1B3 rs4149117 (HR 2.024, 95% CI:1.013-4.044, P=0.046), the CCC-CCC alleles in SLC22A5 haplotype (HR 2.603, 95% CI: 1.216-5.573, P=0.014), and the GC-GC alleles in the IL4 R haplotype (HR 7.131, 95% CI:1.518-33.496, P=0.013) were predictive for OS. This shows that polymorphisms in the pharmacokinetic and pharmacodynamic pathways of sunitinib are associated with survival in GIST. This may help to identify patients that benefit more from treatment with sunitinib.
AuthorsJ S L Kloth, M C Verboom, J J Swen, T van der Straaten, S Sleijfer, A K L Reyners, N Steeghs, H Gelderblom, H J Guchelaar, R H J Mathijssen
JournalThe pharmacogenomics journal (Pharmacogenomics J) Vol. 18 Issue 1 Pg. 49-55 (01 2018) ISSN: 1473-1150 [Electronic] United States
PMID28117434 (Publication Type: Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't)
Chemical References
  • Antineoplastic Agents
  • Biomarkers, Tumor
  • Sunitinib
Topics
  • Antineoplastic Agents (therapeutic use)
  • Biomarkers, Tumor (genetics)
  • Female
  • Gastrointestinal Neoplasms (etiology, genetics, mortality)
  • Gastrointestinal Stromal Tumors (drug therapy, genetics, mortality)
  • Humans
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide (genetics)
  • Progression-Free Survival
  • Sunitinib (therapeutic use)

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!


Choose Username:
Email:
Password:
Verify Password:
Enter Code Shown: