The role of BNO69 as a target for inhibiting angiogenesis (blood vessel formation) was published late last year in the prestigious scientific journal Proceedings of the National Academy of Sciences USA (PNAS) and more recently in the scientific journal Physiological Genomics. Recent clinical successes with drugs which inhibit angiogenesis, a key factor in the growth of solid cancers, have intensified the interest of pharmaceutical companies in this area.

More recent findings indicate that BNO69 and molecules that silence its expression may have therapeutic utility in directly targeting cancer cells. Cell-based assays demonstrated that BNO69 silencing molecules curtail the tumorigenic behaviour exhibited by a number of tumour cell types, including, breast and colon cancer. Previously reported animal studies have shown that molecules which silence BNO69 have a profound effect on tumour growth and that BNO69 is potentially an effective drug target for treating breast cancer. In those studies, breast cancer cells that were treated with BNO69 gene-silencing molecules showed a significantly reduced capacity in forming solid tumours in mice. Solid tumours arising from cells treated with BNO69 silencing molecules were over 75% smaller compared to tumours arising from untreated cells. Bionomics has confirmed this data in repeat studies with observed tumour size reductions as high as 94%.

The research team also included Huntsman Cancer Institute scientists Debra Regier, Ph.D.; Jared Higbee; Katrina Lund; Fumio Sakane, Ph.D.; and Stephen M. Prescott, M.D., professor of internal medicine at the University of Utah and executive director of Huntsman Cancer Institute.

The researchers used mice that were bred to have a highly "expressed" -- meaning highly active -- mutant of the Ras oncogene. Such mice were first developed years ago. Prior studies had demonstrated that these mice were very prone to tumors. For the new study, the Hunstman Cancer Institute team deleted the DGK iota gene in these mice and found that they developed few tumors, while mice with an intact DGK iota gene and an activated Ras gene exhibited significantly more tumors.

Topham says his team will now examine more closely the mechanism behind how DGK iota works to inhibit tumor formation.

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