Ras-MAPK pathway as a therapeutic target in cancer--emphasis on bladder cancer.
The Ras-MAPK pathway is important to orchestrating a cell's response to external and internal stimuli. This pathway is commonly dysregulated in cancer, including bladder cancer. Multiple components of this complex pathway have been identified as potential targets for drug development. After initial preclinical studies many drugs targeting the Ras-MAPK pathway are being studied in phase II clinical trials for advanced bladder cancer either alone or in combination with other chemotherapeutic agents. Drugs presently in clinical trials inhibit the tyrosine kinases, including FGFR, EGFR, ERBB2, and PDGF, either through small molecule tyrosine kinase, dual kinase or farnesyltransferase inhibitors. Recent drug patents targeting the Ras-MAPK pathway in cancer are becoming more selective with the potential for improved therapeutic response and better toxicity as compared to the more universal MAPK pathway inhibitors. In the present review we summarize the importance of the Ras-MAPK pathway in cancer with a focus on bladder cancer and discuss current drugs and recent patents (2004-2008) that target this important pathway in bladder cancer.
Dangle
Pankaj P
PP
Department of Urology, The Ohio State University Comprehensive Cancer Center, Columbus, Ohio 43210, USA.
Zaharieva
Boriana
B
Jia
Hongtao
H
Pohar
Kamal S
KS
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D051231:Farnesyltranstransferase / Q000037:antagonists & inhibitors; D006801:Humans; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000502:physiology*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D020794:Receptor Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D018631:ras Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*
D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D051231:Farnesyltranstransferase; D011505:Protein-Tyrosine Kinases; D020794:Receptor Protein-Tyrosine Kinases; D020928:Mitogen-Activated Protein Kinases; D018631:ras Proteins