Poster

Combination treatment by AKT inhibitor ARQ 092 and Sorafenib
in a cirrhotic rat model with hepatocellular carcinoma
Zuzana Macek Jilkova1,2, Ayca Zeybek Kuyucu1,2, Keerthi Kurma1,2, Séyédéh Tayébéh Ahmad Pour1,2, Gaël S Roth1,2,3, Giovanni Abbadessa4, Yi Yu4,
Vincent Leroy1,2,3, Patrice Marche1,2 and Thomas Decaens1,2,3
1Université Grenoble Alpes; 2Institute for Advanced Biosciences, Research Center UGA / Inserm U 1209 / CNRS 5309;3 Clinique Universitaire d’Hépato-gastroentérologie,CHU Grenoble, France; 4ArQule Inc, USA
METHODS
BACKGROUND RESULTS - in vivo
•Hepatocellular carcinoma is the 5th most common
cancer worldwide and the 2nd cancer related death
•Developed on cirrhosis in 90% of the cases
•Only one approved drug in advanced cases:
sorafenib
•PI3K/AKT/mTOR pathway activated in HCC >50%
of the cases and in fibrogenesis
•Combination of Sorafenib and ARQ 092 exerted additive effect in controlling tumor
progression, reduced angiogenesis and improved liver fibrosis.
•Our results confirm the importance of targeting AKT in hepatocellular carcinoma.
OBJECTIVES
CONCLUSIONS
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in vivo - Treatment protocol
in vitro -Cell viability and migration was tested on HepG2,
Hep3B, HUH7, PLC/PRF5
•Oral gavage daily:
Sorafenib (10 mg/kg) continuously
ARQ 092 (15 mg/kg) 5 days ON/ 9 days OFF
RESULTS - in vitro
Benefit < 3
months
ARQ 092
•T2-weighted MRI:
diameter of 10
largest tumors
(representative
image of control rat)
•Synergistic suppression of
cell growth (Hep3B, MTT)* •Reduced migration in additive manner (Hep3B, Scratch assay)*
•Number and size of tumors
on liver surface
•Tumor progression
assessed by MRI
•Fibrosis assessed by Sirius red
•Cell proliferation
in tumor tissue
•Antiangiogenic effect
•Pathway analysis
Western blot qPCR
*Similar results were obtained with HepG2, HUH7 and PLC/PRF5