Transformation of alkylating regimen of thiotepa into tepa determines the disease progression through GSTP1 gene polymorphism for metastatic breast cancer patients receiving thiotepa containing salvage chemotherapy

GSTP1公司 噻替帕 肿瘤科 医学 内科学 单核苷酸多态性 基因型 药物遗传学 化疗 卡培他滨 多西紫杉醇 药理学 癌症研究 生物 癌症 结直肠癌 环磷酰胺 遗传学 基因
作者
Xinna Zhou,Xiaoli Wang,Qingkun Song,Huabing Yang,Xishan Zhu,Jing Yu,Guohong Song,Lijun Di,Jun Ren,Hong Shao,H. Kim Lyerly
出处
期刊:International Journal of Clinical Pharmacology and Therapeutics [Dustri-Verlag]
卷期号:53 (11): 914-922 被引量:4
标识
DOI:10.5414/cp202391
摘要

The shifts to second-line chemotherapy for metastatic breast cancer (MBC) were widely required based on pharmaceutical molecular profiles to reach out precision medicine. The emerging precise treatment of cancer requires the implementation of clarified pharmacogenetic profiles which are capable of elucidating the predictive responses to cancer chemotherapy. Therefore we were interested in the analysis of the roles of single nucleotide polymorphism (SNP) of GSTP1 (glutathione S-transferase pi 1 gene) alleles to identify pharmacological links with predictors of clinical responses and toxicities.93 MBC patients receiving thiotepa plus docetaxel chemotherapy were enrolled in this study. Optimized CYP3A5, CYP2B6, and GSTP1 were predominantly selected as candidate genes and their three SNPs (CYP2B6 G516T, CYP3A5 A6986G, and GSTP1 A313G) were genotyped by matrix-assisted laser desorption ionization/time of flight (MALDI-TOF) mass spectrometry. Progression-free survival (PFS), disease control rate, and chemo-related toxicities were recorded.GSTP1 A313G (rs1695) was identified to be related with disease progression. In particular, patients harboring AG/GG genotype demonstrated a statistically longer PFS than those with AA. Multivariate analysis confirmed that AG/GG genotype was associated with both clinical responses and liver-localized metastatic lesions. No correlation was found between these three SNPs and chemotherapy-induced toxicity.These results suggest that the GSTP1 polymorphism is a novel prognostic marker for clinical response to thiotepa-containing chemotherapy regimens. Such evidence could provide insight into the role of pharmacogenetics to deprive of biases in shifting regimens solely by empirical choices.
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