Vertex makes progress with novel anticancer class
chromosomes of cells divide and separate during cell division.
Researchers have spent many years trying to identify the cellular
mechanisms that are involved in keeping this process under control
in the hope of identifying new drug targets for cancer.
Recently, it has been established that a class of enzymes known as the Aurora kinases (also known as BTAK and STK15) plays a pivotal role in making sure that cells divide without any chromosomal or genetic errors that could lead to mutations and cancer. If this control mechanism goes wrong, for example if the enzymes are expressed in inappropriately high levels, then cancer can result.
Scientists at Vertex Pharmaceuticals reported yesterday in the journal Nature Medicine (March issue), for the first time, that a selective small molecule inhibitor of the Aurora kinases profoundly reduces tumour growth in cancer models.
"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 down-regulating p53, one of the body's natural tumour suppressors," said the company.
Vertex' small molecule Aurora kinase inhibitor VX-680 blocked cancer cell proliferation in the animal study, and also triggered cell death in a broad range of tumour cell types. And data from in vivo xenograft models - in which animals carry human tumours - indicated that VX-680 achieved complete inhibition of tumour growth at well-tolerated doses, while in some instances regression was observed.
In the study, Vertex researchers reported that VX-680 induced tumour regression of 22 per cent in a human pancreatic xenograft model and of 56 per cent in human colon cancer xenografts.
Two members of the Aurora kinase family, Aurora A and B, are overexpressed in a number of human tumours including pancreas, colon, ovarian, and breast cancer. Vertex said it plans to start trials of a lead Aurora kinase inhibitor in humans before the end of the year.
Vertex has a broad-ranging agreement with Switzerland's Novartis for the discovery and development of kinase inhibitors, but may elect to take the development of VX-680 on its own, according to the company.
Meanwhile, AstraZeneca also has a programme researching small molecule Aurora kinase inhibitors for cancer, and presented its initial preclinical work in this area at last year's American Association of Cancer Research annual meeting in Boston, US.
