Legumain is a protein that is linked to aggressive prostate cancer: the more of this protein in the cancer, the more likely it is to be aggressive, and the worse the outcomes are for men.
But inhibiting legumain with chemicals can stop prostate cancer growth and spread, while, importantly, leaving other healthy cells unaffected.
In this project, we funded Dr Richard Williams to learn more about how legumain works in prostate cancer, and turn this knowledge into potential new ways to treat advanced disease.
Designing legumain inhibitors for better prostate cancer treatment
Dr Williams’ team had previously designed some inhibitors of legumain, but in this project, a medicinal chemist took on the job of optimizing these chemicals, so they are as powerful and efficient as possible. Only then, would the chemicals be able to go on to the next stages of becoming drugs.
These new chemicals would also be valuable tools for the team in learning about how legumain works, and understanding what makes prostate cancer aggressive in some men.
A potential link with immunotherapy
To date, we have developed the most potent and 'drug-like' legumain-inhibitor in the field. In addition, there is on-going research looking at the role of Legumain in cancer immunity. This could be a very exciting field of research.
By the end of the project, the team had developed a panel of the world’s most advance legumain inhibitor chemicals.
Using a range of experimental techniques, like looking at the knock-on effect of these chemicals in cancer cells, they found new links with legumain and other processes which may be involved in prostate cancer. These in turn could represent new ways to treat prostate cancer, either alone or in combination with the legumain inhibitors.
For example, legumain seems to be linked with how the immune system can work against men, and start encouraging tumours to grow. This may mean anti-legumain drugs could represent a promising new kind of immunotherapy to treat aggressive prostate cancer.
Exploring a wealth of new drug targets
The teams next goal is to delve further into the complicated relationship between legumain and other cancer processes.
They’ve already gained more funding to create inhibitors for another protein, called LSD1, and see if these could be used alongside legumain inhibitors to have an even greater effect.
Finally, they’re already carrying out more research on the promising link between legumain and the immune system.