BACKGROUND/AIM: Sorafenib is currently the only medical treatment with proven efficacy against hepatocellular carcinoma (HCC). HCC cell lines display heterogeneous sensitivity to sorafenib, but little is known about the sensitivity of clinical tumors. We aimed to examine this aspect. MATERIALS AND METHODS: Using experimental tumors generated in nude mice, we set up a technique for short-term culture of HCC fragments. We applied this technique to six human HCC samples obtained from surgical resection. RESULTS: HCC fragments in culture retain their morphology and viability for at least 48 h, permitting an in vitro analysis of the effect of sorafenib on the Extracellular signal-regulated kinase (ERK) cascade. HCC exhibit heterogeneous individual responses, ranging from potent inhibition to paradoxical activation of this oncogenic cascade. CONCLUSION: Our observations highlight the heterogeneous sensitivity of HCC to sorafenib, and point to the potential interest of short-term culture of tumor fragments for personalizing the medical treatment of HCC.
BACKGROUND/AIM: Sorafenib is currently the only medical treatment with proven efficacy against hepatocellular carcinoma (HCC). HCC cell lines display heterogeneous sensitivity to sorafenib, but little is known about the sensitivity of clinical tumors. We aimed to examine this aspect. MATERIALS AND METHODS: Using experimental tumors generated in nude mice, we set up a technique for short-term culture of HCC fragments. We applied this technique to six human HCC samples obtained from surgical resection. RESULTS: HCC fragments in culture retain their morphology and viability for at least 48 h, permitting an in vitro analysis of the effect of sorafenib on the Extracellular signal-regulated kinase (ERK) cascade. HCC exhibit heterogeneous individual responses, ranging from potent inhibition to paradoxical activation of this oncogenic cascade. CONCLUSION: Our observations highlight the heterogeneous sensitivity of HCC to sorafenib, and point to the potential interest of short-term culture of tumor fragments for personalizing the medical treatment of HCC.
Authors: Elisabeth M Haberl; Rebekka Pohl; Lisa Rein-Fischboeck; Susanne Feder; Christopher J Sinal; Astrid Bruckmann; Marcus Hoering; Sabrina Krautbauer; Gerhard Liebisch; Christa Buechler Journal: Int J Mol Sci Date: 2019-12-30 Impact factor: 5.923