New data suggests that as many as one in two of us will suffer from cancer at some point in our lives and whilst treatment is improving, prognosis is still very bad for many cancer types. Cancer in the brain manifests itself as a tumor, an out-of-control mass of brain cells that even develops its own blood supply as it expands. As many as 80,000 people are expected to be diagnosed with a brain tumor this year in the USA alone.
The 3D structure of cromakalim. Prof. Marc Diederich and his team used pre-existing moleucles such as cromakalim as a template to design new ones to target brain tumor cells. (Courtesy of Jynto [CC0], via Wikimedia Commons)
How do scientists come up with new treatments?
Firstly, a target must be chosen. In this case, the most common type of brain tumor is a glioma, originating from glial cells – target identified. Next, a molecule must be proposed to use as a drug. Out of the millions of options available, it must be decided whether to test chemicals that already exist or to specifically design new molecules.
Prof. Marc Diederich and his team at the LBMCC spend a lot of their time sifting through what already exists. They test thousands of different, naturally-occurring molecules just in case they have an effect on cancer cells. Every so often it works and one of the molecules tested will be effective.
The other option is to take molecules that we know interact with cells we want to target and tweak their structure slightly to hopefully make them more aggressive against the cancer. To create new molecules in this way, the LBMCC teamed up with researchers from Austria, Belgium and Korea for a cross-disciplinary collaboration.
The group took two types of molecules (cromakalim and ureas/thioureas) that are known to affect certain human cells that have a similar function to those we find in the brain. They looked at the physical structures of these molecules and designed a series of new ones taking different bits of each of them. Of the 18 resulting hybrid molecules, one was a winner.
Too new to name
The successful molecule, currently named compound 18, is efficient at stopping brain cancer cell growth without affecting healthy cells. Compound 18 does this by blocking the activity of certain genes such as SIRT1 and SIRT2 that are known to be necessary in tumor survival.
The LBMCC team have so far demonstrated the effects of compound 18 in glial cell models and zebrafish. The next step will be to run further in vivo tests in the hopes of moving towards future clinical trials.