BACKGROUND: Hepatocellular carcinoma (HCC) is the fifth most common malignancy worldwide. Unresectable disease patients have median survival of few months. There is a substantial need for novel treatments for patients with advanced HCC. AIM: To provide an update review of mechanism of hepatocarcinigenesis and systemic therapies for HCC and the relevant role of Sorafenib in patients with advanced disease. METHODS: A Medline search was performed to identify pertinent original research and review articles. Selected references in these articles were also evaluated. RESULTS: Systemic chemotherapy for HCC has been quite ineffective. Preclinical studies demonstrated that Raf/MAPK-ERK kinase (MEK)/Extracellular signal regulated kinase (ERK) pathway has a role in HCC. HCC tumours are highly vascularized and vascular endothelial growth factor (VEGF) augments HCC development and metastasis. Sorafenib blocks tumour cell proliferation by targeting Raf/MEK/ERK signalling and exerts an antiangiogenic effect by targeting VEGF receptors-2/3 and platelet derived growth factor receptor beta tyrosine kinases. CONCLUSIONS: Currently available therapies are not effective for patients with advanced HCC. Sorafenib has demonstrated for the first time to prolong survival in patients with advanced HCC, and it is the new reference standard for systemic treatment in these patients.
BACKGROUND:Hepatocellular carcinoma (HCC) is the fifth most common malignancy worldwide. Unresectable disease patients have median survival of few months. There is a substantial need for novel treatments for patients with advanced HCC. AIM: To provide an update review of mechanism of hepatocarcinigenesis and systemic therapies for HCC and the relevant role of Sorafenib in patients with advanced disease. METHODS: A Medline search was performed to identify pertinent original research and review articles. Selected references in these articles were also evaluated. RESULTS: Systemic chemotherapy for HCC has been quite ineffective. Preclinical studies demonstrated that Raf/MAPK-ERK kinase (MEK)/Extracellular signal regulated kinase (ERK) pathway has a role in HCC. HCC tumours are highly vascularized and vascular endothelial growth factor (VEGF) augments HCC development and metastasis. Sorafenibblocks tumour cell proliferation by targeting Raf/MEK/ERK signalling and exerts an antiangiogenic effect by targeting VEGF receptors-2/3 and platelet derived growth factor receptor beta tyrosine kinases. CONCLUSIONS: Currently available therapies are not effective for patients with advanced HCC. Sorafenib has demonstrated for the first time to prolong survival in patients with advanced HCC, and it is the new reference standard for systemic treatment in these patients.
Authors: Roberto Gedaly; Paul Angulo; Jonathan Hundley; Michael F Daily; Changguo Chen; Alvaro Koch; B Mark Evers Journal: Anticancer Res Date: 2010-12 Impact factor: 2.480
Authors: Melanie B Thomas; Deborah Jaffe; Michael M Choti; Jacques Belghiti; Steven Curley; Yuman Fong; Gregory Gores; Robert Kerlan; Phillipe Merle; Bert O'Neil; Ronnie Poon; Lawrence Schwartz; Joel Tepper; Francis Yao; Daniel Haller; Margaret Mooney; Alan Venook Journal: J Clin Oncol Date: 2010-08-02 Impact factor: 44.544
Authors: R Cabrera; D S Pannu; J Caridi; R J Firpi; C Soldevila-Pico; G Morelli; V Clark; A Suman; T J George; D R Nelson Journal: Aliment Pharmacol Ther Date: 2011-05-23 Impact factor: 8.171
Authors: R Cabrera; A R Limaye; P Horne; R Mills; C Soldevila-Pico; V Clark; G Morelli; R Firpi; D R Nelson Journal: Aliment Pharmacol Ther Date: 2012-10-24 Impact factor: 8.171
Authors: Alexander Mitsos; Ioannis N Melas; Paraskeuas Siminelakis; Aikaterini D Chairakaki; Julio Saez-Rodriguez; Leonidas G Alexopoulos Journal: PLoS Comput Biol Date: 2009-12-04 Impact factor: 4.475
Authors: Alok R Singh; Shweta Joshi; Adam M Burgoyne; Jason K Sicklick; Sadakatsu Ikeda; Yuko Kono; Joseph R Garlich; Guillermo A Morales; Donald L Durden Journal: Mol Cancer Ther Date: 2016-08-05 Impact factor: 6.261