The vast majority of deaths from cancer result from its progressive spread to vital organs, known as metastasis. According to a press release from the Cardiff University, up to 12,000 patients a year develop metastatic breast cancer, often several years after initial diagnosis of a breast lump. Recently, researchers identified a previously unknown critical role for a potential cancer causing gene, Bcl3, in metastatic breast cancer cells.
“We showed that suppressing this gene reduced the spread of cancer by more than 80%,” Dr. Richard Clarkson, from Cardiff University’s European Cancer Stem Cell Research Institute, said the press release.
The researchers’ next step was to find a way to suppress Bcl3 pharmacologically. Although there have been great improvements in therapy of early stage breast cancer, Dr. Clarkson said, the current therapeutic options for patients with late stage metastatic disease are limited.
“There is therefore a clear unmet clinical need to identify new drugs to reverse, or at least to slow down, disease progression” he added. Dr. Clarkson’s team joined researchers Dr. Andrea Brancale and Dr. Andrew Westwell, from the Cardiff University School of Pharmacy and Pharmaceutical Sciences, to develop small chemical inhibitors of the Bcl3 gene.
The group identified a pocket on the surface of Bcl3, essential to its function, through a computer aided modeling of how the gene functions inside the cell. By screening a virtual compound library for chemicals that could fit inside this pocket, using state-of-the-art computer software, they identified a drug candidate that potently inhibits Bcl3. The compound was then trialed on mice with metastatic disease. The resulting effect was that the drug completely inhibited the development of the mice’s metastatic tumors.
With financial backing from Tiziana Pharmaceuticals, a UK–based biotechnology start-up company, work is now underway to progress the compound to clinical trials. The aim is to develop a therapeutic agent capable of blocking metastatic disease in breast cancer and a variety of tumour types.