Transforming growth factor beta (TGFβ) is a multi-functional cytokine that regulates a wide variety of cellular processes, such as proliferation, differentiation and apoptosis. The role of TGFβ in breast cancer is complex. In the early stages of the disease TGFβ functions as a tumour suppressor, but later the protein switches to a prometastatic factor, suggesting that the inhibition of TGFβ activity may be of benefit in the treatment of stage IV metastatic disease. There is much interest at the present time in the development of strategies to inhibit the TGFβ signalling pathway for the treatment of metastatic cancer and other diseases.
We are using an in silico approach to identify small molecules capable of disrupting the TGFβ signalling pathway. In particular, we are searching for compounds with the ability to bind to the same site on the type II receptor (TβR-II) as TGFβ itself, thus preventing recruitment of the type I receptor, effectively blocking the ensuing signalling cascade.