Functional analysis and molecular targeting of aurora kinases a and B in advanced melanoma

Over the past few years, high-throughput analyses have provided important novel insights into molecular pathways that play a crucial role in the progression from early to advanced melanoma, and at the same time, they have led to the identification of genes that as part of melanoma progression are upregulated in advanced melanoma. In the present study, we provide evidence that Aurora kinases A and B, 2 key regulators of M phase progression, are upregulated to high levels with progression from melanoma in situ to primary and metastatic melanoma and that inhibiting the expression of these 2 genes by RNA interference or blocking their function with an Aurora kinase-specific small-molecule inhibitor severely impairs melanoma cell proliferation and cell cycle progression and induces melanoma cell apoptosis. In addition, we present the results of systemic treatment of human melanoma xenografts with an Aurora kinase small-molecule inhibitor as well as Aurora kinase targeting vectors.