Angiogenesis and signaling through the RASlRAF/mitogen-activated protein/extracellular signal-regulated kinase (ERK) kinase (MEK)/ERKcascade have been reported to play important roles in the development of hepatocellular carcinoma (HCC). Sorafenib (Nexavar), a novel bi-aryl urea SAY 43-9006, is an orally administered multikinase inhibitor with activity against RASIRAF kinases multikinase inhibitor with activity against RAP kinases and several receptor tyrosine kinases, including vascular endothelial growth factor receptor (VEGFR), platelet-derived growth factor receptor (pDGFR), FLT3, Ret, and c-Kit. It is involved in angiogenic pathway and cell proliferation. Sorafenib has demonstrated potent anti-tumor activity in in vitro studies, preclinical xenograft models of different tumor types and human clinical trials. This review summarizes the history of sorafenib from its discovery by the medicinal chemistry approach through to clinical development and ongoing trials on the combination between sorafenib and trans-arterial chemoembolization (TACE) in HCC patients.
Sorafenib (BAY 43-9006) in hepatoccellular carcinoma patients: from discovery to clinical development.
RIZZO, ANNALISA;SCIORSCI, Raffaele Luigi;
2012-01-01
Abstract
Angiogenesis and signaling through the RASlRAF/mitogen-activated protein/extracellular signal-regulated kinase (ERK) kinase (MEK)/ERKcascade have been reported to play important roles in the development of hepatocellular carcinoma (HCC). Sorafenib (Nexavar), a novel bi-aryl urea SAY 43-9006, is an orally administered multikinase inhibitor with activity against RASIRAF kinases multikinase inhibitor with activity against RAP kinases and several receptor tyrosine kinases, including vascular endothelial growth factor receptor (VEGFR), platelet-derived growth factor receptor (pDGFR), FLT3, Ret, and c-Kit. It is involved in angiogenic pathway and cell proliferation. Sorafenib has demonstrated potent anti-tumor activity in in vitro studies, preclinical xenograft models of different tumor types and human clinical trials. This review summarizes the history of sorafenib from its discovery by the medicinal chemistry approach through to clinical development and ongoing trials on the combination between sorafenib and trans-arterial chemoembolization (TACE) in HCC patients.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
