In Nature Medicine, researchers from Vertex Pharmaceuticals Incorporated have demonstrated for the first time that a selective small molecule inhibitor of the Aurora kinases, VX-680, profoundly reduces tumour growth in cancer models. Aurora kinases are known to be overexpressed in many tumour types, including colon cancer, breast cancer, and leukemia.

Research into the function and activity of Aurora kinases over the past several years has suggested that they may play multiple roles in the development and progression of cancer, by acting as regulators of cell proliferation, by transforming normal cells into cancer cells, and by downregulating p53, one of the body’s natural tumour suppressors.

In the study, the small molecule Aurora kinase inhibitor VX-680 blocked cancer cell proliferation, and also triggered cell death in a broad range of tumour cell types. Data from in vivo xenograft models indicated that VX-680 achieved complete inhibition of tumour growth at well-tolerated doses, and in some instances tumour regression was observed. The report suggests that Aurora kinase inhibition provides a promising, novel approach for the treatment of multiple human malignancies.

“ Aurora kinases represent a potentially important class of targets for the future treatment of cancer, and we have now demonstrated for the first time that a small molecule Aurora kinase inhibitor not only blocks tumour cell proliferation but also induces tumour cell death,” commented Karen Miller, director of Biology, Vertex Europe and senior author of the study. “The ability of VX-680 to cause tumour regression is particularly exciting.”

“ VX-680 has demonstrated promising results in a range of tumour types,” said Peter Mueller, chief scientific officer of Vertex. “Inhibition of Aurora kinases represents a novel approach to cancer therapy, and we look forward to the evaluation of Aurora kinase inhibitors in the clinic in 2004.”

Aurora kinases (also known as BTAK and STK15) are a family of serine-threonine kinases that have been linked to tumourigenesis. Aurora kinases, which play a central role in controlling cell division, are disregulated in many types of human cancer, like leukemia, colon and breast cancer. Overexpression of Aurora kinase has been shown to promote transformation of normal cells into cancer cells, and decreased Aurora kinase activity is associated with enhanced function of the body’s normal tumour suppressor genes. Amplification of Aurora genes is associated with progression of colorectal cancer and poor prognosis in certain types of breast cancer.

Cancer is the second leading cause of death in the US; more than 1 million solid tumour cancers are diagnosed in the US annually, with approximately 500,000 deaths.

Cancer cells typically contain mutations in a number of genes, which ultimately results in uncontrolled cell growth and tumour metastasis. As enzymes specific for and essential to cell growth and division, Aurora kinases hold the potential to be important control points for slowing the growth and spread of tumours.