Aurora kinases are key regulators of cell division and proliferation; the enzyme helps the dividing cell share its genetic material with the daughter cells. There are 3 different classes, A, B and C. Over expression of aurora kinase has been associated with several different cancers including breast, colon, bladder, pancreatic, ovarian and leukemia. Indeed, over expression of aurora kinase A has been linked to poor prognosis in breast cancer.
It is not yet known whether the pathway is critical to aberrant signaling, although inhibition has been shown to slow the uncontrolled cell growth that characterizes cancer. Aurora kinases do, however, appear to map to chromosome regions that are frequently altered in tumours. In preclinical models, over expression leads to aggressive tumour growth and resistance to cytotoxic agents.
The concept of aurora kinase inhibitors is, therefore, an avenue well worth researching as a potential new class of anti-cancer agents. Preclinically, some of the initial prototypes have been shown to block the final stages of cell division, resulting in apoptosis and cancer cell death.
Three of the leading aurora kinase inhibitors in early testing at the moment are from Vertex (VX-680), Riga (R-763) and Millennium (MLN-8054). Interestingly, both the Vertex and Riga compounds have been licensed out to Merck and Serono, for deals of $350M and $160M, respectively. There are a number of other agents in preclinical development at AstraZeneca, Sunesis, Entremed, Boehringer Ingelheim, Cyclacel and others, so the field is a busy and active one, competition wise.
It will be interesting to follow the development of this new class of agents and see whether the concept lives up to the promise. At the recent AACR meeting in Philadelphia there were a number of abstracts on aurora kinases and there will be surely more to come at the 2006 annual meeting in April (click here).
Watch this space!