Molecular subtype and response to dasatinib, an Src/Abl small molecule kinase inhibitor, in hepatocellular carcinoma cell lines in vitro

• DOI: 10.1002/hep.26223
• Publication Date: 2013-01-09T05:57:36Z
• Authors: Richard S. Finn; Alexey Aleshin; Judy Dering; Peter Yang; Charles Ginther; Amrita Desai; Danyun Zhao; Erika von Euw; Ronald W. Busuttil; Dennis J. Slamon
• Keywords: ABL

Hepatocellular carcinoma (HCC) is the fifth most common malignancy and third leading cause of cancer death worldwide. Recently, multitargeted kinase inhibitor sorafenib was shown to be first systemic agent improve survival in advanced HCC. Unlike other malignancies such as breast cancer, which molecular subtypes have been clearly defined (i.e., luminal, HER2 amplified, basal, etc.) tied effective therapeutics (hormone blockade trastuzumab, respectively), HCC this translational link does not exist. Molecular profiling studies human identified unique disease. We hypothesized that a panel cell lines would maintain characteristics clinical disease could then used model for novel therapeutics. Twenty were collected RNA analyzed using Agilent microarray platform. Profiles from vitro recapitulate previously described subgroups material. Next, we evaluated whether subgroup predictive value response Src/Abl dasatinib. The results demonstrate sensitivity dasatinib associated with progenitor subtype. Dasatinib at inducing cycle arrest apoptosis "progenitor-like" but resistant lines.These findings suggest line models background subtype may important selecting patients therapies. In addition, it highlights potential role Src family signaling