Transcriptomics

Dataset Information

0

A Window of Opportunity Study of Valproic Acid in Breast Cancer Testing a Gene Expression Biomarker


ABSTRACT: Purpose: Valproic acid(VPA) has anti-cancer activity attributed to histone deacetylase inhibition(HDACi). We published the Genomically–Derived Sensitivity Signature for VPA(GDSS-VPA), a gene expression biomarker predicting breast cancer sensitivity to VPA in vitro and in vivo. We conducted a window-of-opportunity study examining the tolerability of VPA and the ability of the GDSS-VPA to predict biologic changes in breast tumors from VPA. Methods: Eligible women had untreated breast cancer with breast tumors over 1.5 cm. After a biopsy, women took VPA for 7-12 days, increasing from 30mg/kg/day PO divided BID to a maximum of 50mg/kg/day. After VPA treatment, serum VPA level was measured followed by breast surgery or a biopsy. Tumor proliferation was assessed by Ki-67 immunohistochemistry. Peripheral blood mononuclear cells(PBMCs) histone acetylation was assessed by Western blot. Results: Thirty women were evaluable. The median age was 54(range 31-73). 52% of women tolerated 50mg/kg/day, but 10% missed more than two doses due to adverse events(AEs). Grade 3 AEs included one patient with vomiting and diarrhea and one with fatigue. The end serum VPA level correlated with change in PBMC histone acetylation(rho=0.451, p=0.024). 50% of women with triple-negative breast cancer(TNBC) had a Ki-67 reduction of at least 10%, compared with 17% of other women. GDSS-VPA correlated with a Ki-67 decrease of at least 10%(AUC 0.66). Conclusions: Most women tolerate VPA. VPA treatment caused a decrease in proliferation of breast tumors. The genomic biomarker correlated with decreased proliferation. HDACi is a valid strategy for drug development in TNBC using gene expression biomarkers.

ORGANISM(S): Homo sapiens

PROVIDER: GSE83530 | GEO | 2016/12/17

SECONDARY ACCESSION(S): PRJNA326262

REPOSITORIES: GEO

Dataset's files

Source:
Action DRS
Other
Items per page:
1 - 1 of 1

Similar Datasets

2020-10-12 | PXD021912 | JPOST Repository
2018-10-26 | PXD003551 | Pride
2015-08-31 | E-GEOD-65297 | biostudies-arrayexpress
2011-07-01 | E-GEOD-26544 | biostudies-arrayexpress
2024-04-13 | PXD037513 | Pride
2016-04-07 | E-MTAB-3764 | biostudies-arrayexpress
2019-07-20 | E-MTAB-6752 | biostudies-arrayexpress
2015-08-31 | GSE65297 | GEO
2022-05-10 | GSE200106 | GEO
2024-04-07 | E-MTAB-12279 | biostudies-arrayexpress