Background to the project
Early hormone-dependent prostate cancer can be treated surgically, by radiation and by hormone-blocking drugs. While the majority of men with prostate cancer respond to treatment, a large proportion can relapse and progress to advanced stage prostate cancer that is resistant to the effects of the hormone-blocking drugs. The researchers identified a protein called IKKα that is found in higher levels in patients with advanced prostate cancer that appears to be key to its development. They made completely new drug-like compounds that can prevent IKKα from working and which have the potential to turn off the signals that maintain the cancer’s survival.

What they set out to do
This was a totally new style of treatment that had never been tried before in the clinic. However, their compounds required further refinement to work as a daily oral dose. The team worked with chemists to make better compounds, biologists to assess how effective the compounds were in prostate cancer cells, analytical and formulation scientists to assess the ‘drug-like’ properties and medics to advise on clinical aspects. Through an iterative process that involved making, testing, remaking, retesting and optimising compounds they’ve developed a series of IKKα inhibitors with high potency and good selectivity that stops the growth and survival of prostate cancer cells.

What they found out
Their best compound so far, SU1349 meets all the criteria towards assessment in animal models, except for good water solubility to enable oral dosing. They’ve shown that compounds that stop IKKα from working can prevent growth and survival of prostate cancer cells, and in a preliminary study in mice they’ve shown that tumour regression takes place. The solubility of SU1349 is currently being worked on to allow it to be taken orally. Once they’ve shown that the compounds are effective in mouse models of Prostate Cancer, they want to licence this work for preclinical and clinical development.       

How this will benefit men
This drug is still at the early stages and it could take another decade of testing and trials before it becomes available to patients. However, we urgently need new treatments for advanced prostate cancer, as existing drugs can only extend survival by 3-9 months. Preventing IKKα from working could stop prostate cancers from becoming hormone resistant and increase survival times even more.


Institution
- Strathclyde Institute for Pharmacy and Biological Sciences, Glasgow
Researcher - Professor Simon Mackay
Grant award - £249,289
Duration - 2013-2016
Reference - PG12-27 Mackay