Sometimes two brilliant minds find each other in such specific research areas that it makes real the possibility of aligned mental pathways actively seeking each other in the universe. Such is the coming together of two Rhodes academics: Professor Adrienne Edkins and Dr Clint Veale, who are working on novel drug research for cancer in what is known as the Fragment Project.
Prof Edkins is from the Department of Biochemistry and Microbiology. She holds a SARChI Chair in Molecular and Cell Biology of the Eukaryotic Stress Response and was awarded the Vice-Chancellor’s Distinguished Research Medal this year. Dr Clint Veale from the Faculty of Pharmacy did his PhD in medicinal chemistry through the Department of Chemistry.
Researching in different disciplines they were both looking for what Prof Edkins describes as “a specific glint of a needle” in the proverbial haystack of cancer. The specific glint is a protein, known as a receptor, which can be used to target an extremely aggressive and common form of breast cancer in southern Africa, called triple-negative breast cancer.
Unlike other types of breast cancer, which are hormone responsive and treatable, there are currently no targeted treatments for triple-negative breast cancer. There is therefore a pressing clinical need to find ways of treating it, over and above the improvements in health brought about by prevention and early screening.
Cancer, in general, is very difficult to treat because it is about our own cells turning against us, a mutation of our genetics, as Prof Edkins explains: “There is an evolutionarily-conserved system in all cells where a stress response kicks in whenever the cells are under physical stress. The system is a positive survival response but it is problematic in the presence of cancer, as it prevents the cancer cell from dying because it activates a protective stress response. It doesn’t differentiate and therefore in the presence of cancer, the cell effectively sabotages its own survival.”
“Until we find the receptor that regulates triple-negative breast cancer, there is nothing for the anti-cancer drugs to target and therefore the cancer is able to spread unstoppably at this stage,” adds Dr Veale.
The thrust of the Fragment Project is therefore to find new ways of thinking about drug discovery, called fragment-based drug discovery.
Dr Veale’s approach on how to tackle this was developed from his Master’s in Biological Mass Spectrometry at Edinburgh University, Scotland. He was familiar with their spectrometry facility, one of the best of its kind in the world, where researchers are able to screen for drug-like molecular fragments that are able to bind to specific proteins. We can then synthetically modify these fragments in the laboratory to improve their drug efficacy characteristics.
He approached Prof Edkins, a protein target specialist who has done considerable research into triple-negative breast cancer cells and asked if she would be interested in collaborating with him and mass spectrometry specialist, Dr David Clarke, at Edinburgh. She immediately recognised the synergy and the giant leap their mutually advanced research could achieve.
“To get here we first need to understand how the different molecular levels of the cell works, and what the triggers and networks are between the different components,” Prof Edkins explains. “We can then go in and identify a particular node to selectively disable the cell’s response in the presence of cancer, using smaller fragments of drug-like molecules as a base from which to bind and inhibit our protein target.”
“We have been working with a particular protein for four years and we think it could be developed into a possible inhibitor for anti-cancer agents. We were able to grow enough of the protein (in bacteria) to send it over to Edinburgh.
“We are now doing biological studies on this protein and we have evidence to show its levels are higher in cancer cells, and in regulating the activity that cancer cells are dependent on. This makes it a potentially suitable target for the development of anti-cancer drugs, which would be the next step and where we would partner with pharmaceutical companies.”
In July the team was awarded a grant from the Royal Society, Newton Fund to help support the Fragment Project between Rhodes and Edinburgh. One of the purposes of the grant is to promote economic and social development through skills transfer between the two countries.
“These kinds of grants and the SARChI Chair are such a privilege,” says Prof Edkins. “The most precious resource that comes with them is time and the headspace to be creative. It is very difficult to reach the levels of creativity and commitment our research requires if you don’t have space, resources and time.”