TUMOR INITIATING CELLS AND IGF/FGF SIGNALING CONTRIBUTE TO SORAFENIB RESISTANCE IN HEPATOCELLULAR CARCINOMA

ABSTRACT: OBJECTIVE: Sorafenib is effective in hepatocellular carcinoma (HCC), but patients ultimately present disease progression. Molecular mechanisms underlying acquired resistance are still unknown. Herein, we characterize the role of tumor-initiating cells (T-ICs) and signaling pathways involved in sorafenib resistance. DESIGN: HCC xenograft mice treated with sorafenib (n=22) were explored for responsiveness (n=5) and acquired resistance (n=17). Mechanism of acquired resistance were assessed by: 1) Role of T-ICs by in vitro sphere formation and in vivo tumorigenesis assays using NOD/SCID mice, 2) Activation of alternative signaling pathways and 3) Efficacy of anti-FGF and anti-IGF drugs in experimental models. Gene expression (microarray, qRT-PCR) and protein analyses (immunohistochemistry, wes

ORGANISM(S): Homo sapiens

SUBMITTER: Juanjo Lozano 

PROVIDER: E-GEOD-73571 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress