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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.

Publication ,  Journal Article
Zhou, X; Wang, X; Song, Q; Yang, H; Zhu, X; Yu, J; Song, G; Di, L; Ren, J; Shao, H; Lyerly, HK
Published in: Int J Clin Pharmacol Ther
November 2015

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.

Duke Scholars

Published In

Int J Clin Pharmacol Ther

DOI

ISSN

0946-1965

Publication Date

November 2015

Volume

53

Issue

11

Start / End Page

914 / 922

Location

Germany

Related Subject Headings

  • Triethylenephosphoramide
  • Treatment Outcome
  • Time Factors
  • Thiotepa
  • Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
  • Salvage Therapy
  • Risk Factors
  • Retrospective Studies
  • Polymorphism, Single Nucleotide
  • Phenotype
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Zhou, X., Wang, X., Song, Q., Yang, H., Zhu, X., Yu, J., … Lyerly, H. K. (2015). 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. Int J Clin Pharmacol Ther, 53(11), 914–922. https://doi.org/10.5414/CP202391
Zhou, Xinna, Xiaoli Wang, Qingkun Song, Huabing Yang, Xishan Zhu, Jing Yu, Guohong Song, et al. “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.Int J Clin Pharmacol Ther 53, no. 11 (November 2015): 914–22. https://doi.org/10.5414/CP202391.

Published In

Int J Clin Pharmacol Ther

DOI

ISSN

0946-1965

Publication Date

November 2015

Volume

53

Issue

11

Start / End Page

914 / 922

Location

Germany

Related Subject Headings

  • Triethylenephosphoramide
  • Treatment Outcome
  • Time Factors
  • Thiotepa
  • Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
  • Salvage Therapy
  • Risk Factors
  • Retrospective Studies
  • Polymorphism, Single Nucleotide
  • Phenotype