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学科主题: 临床医学
题名:
Transformation of an alkylating regimen of thiotepa into tepa determines disease progression through GSTP1 gene polymorphism in metastatic breast cancer patients receiving thiotepa-containing salvage chemotherapy
作者: Zhou, Xinna1; Wang, Xiaoli1; Song, Qingkun1; Yang, Huabing1; Zhu, Xishan1; Yu, Jing2; Song, Guohong2; Di, Lijun2; Ren, Jun1; Shao, Hong3; Lyerly, Herbert Kim4
关键词: breast cancer ; glutathione S-transferase pi 1gene (GSTP1) ; single nucleotide polymorphism (SNP) ; thiotepa
刊名: INTERNATIONAL JOURNAL OF CLINICAL PHARMACOLOGY AND THERAPEUTICS
发表日期: 2015-11-01
DOI: 10.5414/CP202391
卷: 53, 期:11, 页:914-922
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Pharmacology & Pharmacy
研究领域[WOS]: Pharmacology & Pharmacy
关键词[WOS]: DRUG-METABOLISM ; GLUTATHIONE ; PHARMACOGENOMICS ; ASSOCIATION ; EXPRESSION ; ONCOLOGY ; SURVIVAL ; THERAPY ; ENZYMES ; CYP2B6
英文摘要:

Background: 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. Methods: 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. Results: 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. Conclusions: 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.

语种: 英语
所属项目编号: 81172534 ; SPCHIN1201 ; 2013-q-04
项目资助者: Natural Science Foundation of China ; Suan G. Komen for Cure Foundation ; Youth Foundation of Beijing Shijitan Hospital
WOS记录号: WOS:000365460200002
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/58296
Appears in Collections:北京大学临床肿瘤学院_期刊论文

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作者单位: 1.Duke Univ, Med Ctr, Dept Surg, Durham, NC 27710 USA
2.Capital Med Univ, Beijing Shijitan Hosp, Dept Med Oncol, Beijing Key Lab Therapeut Canc Vaccines,Canc Ctr, Beijing 100038, Peoples R China
3.Peking Univ, Sch Oncol, Beijing Canc Hosp & Inst,Dept Med Oncol, Key Lab Carcinogenesis & Translat Res,Minist Educ, Beijing 100871, Peoples R China
4.Peking Univ, Sch Pharmaceut Sci, Dept Pharm Adm & Clin Pharm, Beijing 100191, Peoples R China

Recommended Citation:
Zhou, Xinna,Wang, Xiaoli,Song, Qingkun,et al. Transformation of an alkylating regimen of thiotepa into tepa determines disease progression through GSTP1 gene polymorphism in metastatic breast cancer patients receiving thiotepa-containing salvage chemotherapy[J]. INTERNATIONAL JOURNAL OF CLINICAL PHARMACOLOGY AND THERAPEUTICS,2015,53(11):914-922.
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