Raf Kinases in Cancer: Roles and Therapeutic Opportunities

Researchers in Vienna, Austria have discovered that Raf kinases play a crucial role in cancer, with the three mammalian RAF proteins (A, B, and CRAF) being activated by the human oncogene RAS. This leads to tumor-promoting functions, mediated by the MEK/ERK pathway, which is associated with proliferation in various human tumors. The study highlights the potential of Raf as a molecular target for anticancer therapy, particularly in melanoma patients, where small-molecule RAF inhibitors have shown unprecedented response rates.

Key Takeaways:

• Raf kinases are conserved, ubiquitous serine/protein kinases hijacked by transforming retroviruses, with three mammalian RAF proteins (A, B, and CRAF) being activated by the human oncogene RAS.
• The kinase-dependent functions of Raf are mediated chiefly by the MEK/ERK pathway, associated with proliferation in a broad range of human tumors.
• Almost 10 years ago, activating BRAF mutations were discovered in a subset of human tumors.
• In the past year, treatment with small-molecule RAF inhibitors has yielded unprecedented response rates in melanoma patients.
• Raf qualifies as an excellent molecular target for anticancer therapy.
• Researchers concluded that BRAF and CRAF play a crucial role in carcinogenesis, and that molecular therapies targeting Raf present both success and challenges.

Statistics:

• 10 years ago, activating BRAF mutations were discovered in a subset of human tumors.
• In the past year, treatment with small-molecule RAF inhibitors has yielded unprecedented response rates in melanoma patients.
• The MEK/ERK pathway is associated with proliferation in a broad range of human tumors.

Sources:

• "Raf kinases in cancer-roles and therapeutic opportunities." Oncogene, 2011;30(32):3477-88.
• Contact info: G. Maurer, Max F Perutz Laboratories, Center for Molecular Biology, University of Vienna, Vienna, Austria.