MEK 1/2 inhibitors in the treatment of hepatocellular carcinoma.
Sorafenib is the only approved systemic treatment for advanced hepatocellular carcinoma patients and all the recently published randomized controlled trials on new systemic drugs have been unsuccessful. This is likely due to a lack of understanding of tumor progression, molecular drivers, and liver toxicity, as well as flaws in trial design. An important signaling pathway in hepatocarcinogenesis is the MEK cascade involved in various cellular responses, including adaptation and survival. A key role in this cascade is played by MEK, of which MEK 1/2 represent the prototypes and an interesting target for new oncological drugs. This review analyzes recent developments and future perspectives on the role of MEK inhibitors in hepatocellular carcinoma treatment.
Gastroenterology Unit, Department of Medical and Surgical Sciences, University of Foggia, Ospedali Riuniti Foggia, Italy.
Antonio
A
Facciorusso
Raffaele
R
Licinio
Brian I
BI
Carr
Alfredo
A
Di Leo
Michele
M
Barone
D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001562:Benzimidazoles / Q000627:therapeutic use; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy*; D004159:Diphenylamine / Q000031:analogs & derivatives / Q000627:therapeutic use; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy*; D048369:MAP Kinase Kinase 1 / Q000037:antagonists & inhibitors*; D048370:MAP Kinase Kinase 2 / Q000037:antagonists & inhibitors*; D009536:Niacinamide / Q000031:analogs & derivatives / Q000627:therapeutic use; D010671:Phenylurea Compounds / Q000627:therapeutic use; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D000077157:Sorafenib; D013449:Sulfonamides / Q000627:therapeutic use
C517975:AZD 6244; D000970:Antineoplastic Agents; D001562:Benzimidazoles; C550600:N-(2,3-dihydroxypropyl)-1-((2-fluoro-4-iodophenyl)amino)isonicotinamide; C544830:N-(3,4-difluoro-2-(2-fluoro-4-iodophenylamino)-6-methoxyphenyl)-1-(2,3-dihydroxypropyl)cyclopropane-1-sulfonamide; D010671:Phenylurea Compounds; D047428:Protein Kinase Inhibitors; D013449:Sulfonamides; D009536:Niacinamide; D004159:Diphenylamine; D000077157:Sorafenib; D048369:MAP Kinase Kinase 1; D048370:MAP Kinase Kinase 2
HCC; MEK; liver cancer; refametinib; sorafenib