TY - JOUR
T1 - Emerging Raf inhibitors
AU - McCubrey, James A.
AU - Steelman, Linda S.
AU - Abrams, Steven L.
AU - Chappell, William H.
AU - Russo, Suzanne
AU - Ove, Roger
AU - Milella, Michele
AU - Tafuri, Agostino
AU - Lunghi, Paolo
AU - Bonati, Antonio
AU - Stivala, Franca
AU - Nicoletti, Ferdinando
AU - Libra, Massimo
AU - Martelli, Alberto M.
AU - Montalto, Giuseppe
AU - Cervello, Melchiorre
PY - 2009/12
Y1 - 2009/12
N2 - Background: The Raf/MAPK kinase/extracellular-signal-regulated kinase pathway is often activated by genetic alterations in upstream signaling molecules. An integral component of this pathway, BRAF, is also activated by mutation, especially in melanoma and thyroid cancers. The Raf/MAPK kinase/extracellular-signal-regulated kinase pathway has profound effects on proliferative, apoptotic and differentiation pathways as well as the sensitivity and resistance to chemotherapeutic drugs. Objectives/methods: This review discusses targeting of Raf which could control abnormal proliferation in cancer and other proliferative diseases. The important roles that genetics plays in the response of patients to Raf inhibitors is also evaluated. We also discuss the rationales for approaches combining Raf inhibitors and chemotherapeutic drugs. Results/conclusions: Various Raf inhibitors have been developed and are being clinically used to treat patients with melanoma, thyroid, hepatocellular and renal cell cancers. Some 'Raf-kinase inhibitors' affect other kinases which are also expressed on malignant cells; yet, these inhibitors have proven useful in the therapy of certain cancer patients. Other more recently developed Raf specific inhibitors have shown success in the treatment of tumors bearing Raf mutations. The development of Raf inhibitors has significantly advanced cancer therapy in the past decade.
AB - Background: The Raf/MAPK kinase/extracellular-signal-regulated kinase pathway is often activated by genetic alterations in upstream signaling molecules. An integral component of this pathway, BRAF, is also activated by mutation, especially in melanoma and thyroid cancers. The Raf/MAPK kinase/extracellular-signal-regulated kinase pathway has profound effects on proliferative, apoptotic and differentiation pathways as well as the sensitivity and resistance to chemotherapeutic drugs. Objectives/methods: This review discusses targeting of Raf which could control abnormal proliferation in cancer and other proliferative diseases. The important roles that genetics plays in the response of patients to Raf inhibitors is also evaluated. We also discuss the rationales for approaches combining Raf inhibitors and chemotherapeutic drugs. Results/conclusions: Various Raf inhibitors have been developed and are being clinically used to treat patients with melanoma, thyroid, hepatocellular and renal cell cancers. Some 'Raf-kinase inhibitors' affect other kinases which are also expressed on malignant cells; yet, these inhibitors have proven useful in the therapy of certain cancer patients. Other more recently developed Raf specific inhibitors have shown success in the treatment of tumors bearing Raf mutations. The development of Raf inhibitors has significantly advanced cancer therapy in the past decade.
KW - Apoptosis
KW - Cancer
KW - ERK
KW - Kinases
KW - MEK
KW - Proliferative disorders
KW - Protein phosphorylation
KW - Raf
KW - Raf inhibitors
KW - Signal transduction
UR - http://www.scopus.com/inward/record.url?scp=71649098951&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=71649098951&partnerID=8YFLogxK
U2 - 10.1517/14728210903232633
DO - 10.1517/14728210903232633
M3 - Article
C2 - 19715444
AN - SCOPUS:71649098951
VL - 14
SP - 633
EP - 648
JO - Expert Opinion on Emerging Drugs
JF - Expert Opinion on Emerging Drugs
SN - 1472-8214
IS - 4
ER -