Researchers describe how new melanoma drug blocks key cancer pathway

BMJ 2010; 341 doi: (Published 20 September 2010) Cite this as: BMJ 2010;341:c5154
  1. Susan Mayor
  1. 1London

    An investigational new drug has a “remarkably” high response rate (81%) in patients with metastatic melanoma, says a recent report in Nature, which describes how the drug inhibits a key signalling pathway in tumour development.

    The drug, PLX4032, inhibits B-RAF kinase, an enzyme that regulates signalling pathways in cells to control cell division and differentiation. B-RAF kinase is the most frequently mutated protein kinase in human cancers.

    The researchers report that it selectively blocks a particular pathway in cells with mutations of the BRAF gene, known to be associated with the development of cancer (Nature, doi:1038/nature09454). When a growth factor binds to its receptor on the surface of the cells, this pathway—made up of a chain of kinase enzymes (RAF, MEK, and ERK)—communicates a signal from the surface to DNA in the cell’s nucleus.

    Once the signal reaches the DNA it triggers production of further proteins that control cell division and differentiation. If any of these proteins are mutated, they can be stuck in the “on” or “off” position. This …

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