St George’s researchers and partners are using a new technique to screen chemical compounds for cancer-fighting properties, with the aim of finding new drug treatments.

Professor Dot Bennett and Dr Becca Collinson from St George’s, and colleagues in Senectus Therapeutics – a company set up by a consortium of researchers to develop cancer-ageing drugs – have struck a deal to access a selection of chemical compounds provided by global pharmaceutical firm AstraZeneca. They aim to find compounds that trigger a form of cancer cell ageing called senescence. The Senectus team will use the world’s first reliable senescence trigger-screening technique, that it developed itself.

Senescent cells are those that, after many rounds of cell growth and division, enter a sleep phase where the normal cell cycle is stopped. This blocks the uncontrolled growth and division of cells, and is a natural mechanism to prevent cancer spreading. However, cancer cells can find ways to trick their way past this block and continue to grow and divide. Understanding the triggers for senescence may reveal molecular targets for drugs to work on, leading to completely new ways to treat cancer.

Prof Bennett and her colleagues set up Senectus in 2008 with a £500,000 grant from Cancer Research UK’s Discovery Committee, and spent two years developing the senescence screening technique.

The technique involves growing cancer cells with a compound, then without the compound, and then using molecular markers to dye the cells’ DNA. An automated scanner then scans each culture and reports whether senescence has been initiated.

AstraZeneca has provided about 250 different compounds at varying concentrations. The full senescence period takes about 10 days. Once the initial screening is done, further tests will be done on those that tested positive, to ensure accurate results.

Senectus has also been testing compounds provided by Cancer Research UK, which has just given another £500,000 to fund two more years of work.

Some of the Cancer Research UK compounds have tested positive and are under further study. 

Following the screening work, Senectus will work with AstraZeneca, Cancer Research UK and other partners to determine how to progress individual compounds, with the aim of eventually developing new cancer drugs.

Prof Bennett said: “It has been exciting to find out that small molecules really can reinduce cell senescence, even in cancers resistant to normal therapies, like metastatic melanoma cells. The active interest from AstraZeneca demonstrates the spreading belief that this is a serious possibility for novel treatments, especially for such resistant cancers. Two other companies have also expressed interest.”

Nicol Keith, Cancer Research UK’s professor of molecular oncology at the University of Glasgow, and coordinator of the Senectus team, added: “To date there has been very little progress in translating laboratory findings into therapeutic targets. By bringing together these expert groups from industry and academia we have the best group of people to speed up development in this area.”

For more on Senectus, go to the website.