Novel targets in solid tumors: MEK inhibitors.
MAPK/ERK kinase (MEK) inhibitors constitute a promising class of novel targeted therapies. Although some of the initial clinical results with these compounds were disappointing, newer agents with more advantageous pharmacokinetic and pharmacodynamic properties have entered clinical trials. Partial responses have been seen in patients with advanced melanoma and pancreatic cancer, along with prolonged stable disease in several tumor types. Rash, diarrhea, edema, and visual disturbances have been common toxicities. With the recent finding that cell lines with B-raf mutations are exquisitely sensitive to these compounds, the possibility of genetic-based patient selection and indiviualized therapy has been raised. Whether these predictions will be borne out in clinical testing remains to be seen.
Messersmith
Wells A
WA
Sidney Kimmel Cancer Center, Johns Hopkins University, Baltimore, MD 21231, USA. wmesser1@jhmi.edu
Hidalgo
Manuel
M
Carducci
Michael
M
Eckhardt
S Gail
SG
D000970:Antineoplastic Agents / Q000627:therapeutic use*; D006801:Humans; D020930:MAP Kinase Kinase Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D009369:Neoplasms / Q000188:drug therapy* / Q000201:enzymology; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*
D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D020930:MAP Kinase Kinase Kinases