studies

HEPATOLOGY, VOLUME 62, NUMBER 1 (SUPPL) AASLD ABSTRACTS 459A
HIF-1α. Alcohol inhibits miR-122 via transcriptional repression
mediated by GRHL2 upregulation.
Disclosures:
Guangping Gao - Stock Shareholder: VoyagerTherapeutics
The following authors have nothing to disclose: Abhishek Satishchandran, Aditya
Ambade, Banishree Saha, Benedek Gyongyosi, Patrick Lowe, Nicita Mehta,
James V. Zatsiorsky, Arvin Iracheta-Vellve, Jia Li, Donna Catalano, Karen Kodys,
Li Zhong, Jun Xie, Shashi Bala, Gyongyi Szabo
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Niclosamide ethanolamine inhibits growth of patient-derived
hepatocellular carcinoma xenografts
Bin Chen 1 , Wei Wei 2 , Mei-Sze Chua 2 , Atul Butte 1 , Samuel K. So 2 ;
1 Institute for Computational Health Sciences, UCSF, San Francisco,
CA; 2 Asian Liver Center, Stanford University, Stanford, CA
Background and Aim Hepatocellular carcinoma (HCC) is a fatal
malignancy with a dismal prognosis. Sorafenib is the only drug
approved for the treatment of advance HCC patients in the last
decade; it is associated with only a modest response rate. The
recent advances in genomics and transcriptomics have led to
large volumes of molecular data for HCC, providing an unprecedented
opportunity to translate these data into more effective
therapeutics. To address the unmet clinical need in HCC, we
leveraged the public large datasets on disease and drug gene
expression signatures to identify drug candidates that may
have yet unidentified anti-tumor efficacy in HCC. Materials and
Methods We created a HCC gene expression signature by
analyzing 250 patient samples from The Cancer Genome Atlas
and validated it using 1624 patient samples from five independent
cohorts. We further identified drug candidates that
can reverse the HCC disease gene expression, from a library
consisting of over 1000 FDA-approved drugs. We identified
niclosamide and other antihelminthics as potential drug candidates
for the treatment of HCC, and evaluated niclosamide and
niclosamide ethanolamine (NEN, a water soluble niclosamide
salt), for their in vitro and in vivo anti-tumor efficacy against
HCC cells and patient-derived HCC xenografts (PDHX). Results
In silico analysis indicated niclosamide could reverse the gene
expression of HCC patients regardless of their etiology and
tumor grade (FDR