(
Delivering a ‘double whammy’ against ovarian cancer
by Claire O’Connell
03/03/17
From left: Dr Graham Cotton, senior R&D group leader, Almac Discovery; Prof Tracy Robson, head of molecular and cellular therapeutics, RCSI; and Prof Tim Harrison, vice-president, discovery chemistry, Almac Discovery. Image: Maxwell Photography
Prof Tracy Robson is collaborating with Almac Discovery on a new, potentially multitasking cancer treatment. Claire O’Connell investigates.
Cancerous tumours can have a few tricks up their sleeves. So, when treating them, it makes sense to target as many as you can. That’s why Prof Tracy Robson of theRoyal College of Surgeons in Irelandis collaborating withAlmac Discoveryon new therapeutics to not only stop a tumour from building its vital blood supply, but also to tackle a ‘reservoir’ of tumour stem cells that resist cancer treatments.
The approach is based on the biology of a naturally occurring protein in the body called FKBPL, and it aims to using the body’s own machinery to deliver a ‘one-two’ to tumours.
“The project evolved from an ongoing collaboration with Almac at Queen’s University Belfast,” explained Robson, who moved from QUB to RCSI last year.
“We identified a protein that could inhibit blood vessel development, and that was the basis for the development of a novel drug that harnesses the activity of that protein. That drug [ALM201] is now in phase one clinical trial in UK.”
The plan is to identify patients with ovarian cancer who are likely to respond to the drug’s actions and develop the trials further, she explained.
Tumour stem cells
But there is another side to the story. The drug may also tackle tumour stem cells, which have the ability to self-renew and which are resistant to current chemotherapy and radiotherapy. They can act as reservoir of tumour cells that can grow back to form the tumour again.
How did they find out that the drug might affect tumour stem cells? “We realised that the protein and the drug targeted a receptor called CD44 on endothelial cells of blood vessels also on cancer stem cells,” explained Robson. “And we have been able to demonstrate that the drug targets cancer stem cells. Our initial data demonstrates that ALM201 can transform these cells so they are no longer resistant to these therapies.”
From left: Prof Tracy Robson, head of molecular and cellular therapeutics, RCSI; Prof Tim Harrison, vice-president, discovery chemistry, Almac Discovery; and Dr Graham Cotton, senior R&D group leader, Almac Discovery. Image: Maxwell Photography
Double whammy
Delivering this ‘double whammy’ to tumours – inhibiting the blood supply and making tumour stem cells less resistant to therapy –potentially gives the drug an extra edge. “Some drugs which target angiogenesis [the process through which a tumour builds its own blood supply] can kill the normal tumour cells and these cancer stem cells remain behind,” explained Robson. “Targeting both would improve the efficacy of our drug.”
The initial focus of the work is on ovarian cancer and shehopes that the work could be extended to other types of tumour, too.
Robson is very familiar with the FKBPL protein at the root of the one-two approach – she started working on it during her PhD in the 1990s. “I have built my career really around this protein, trying to understand its function and we have harnessed that activity,” she said. “It’s really lovely to see it coming to translational fruition, but it also emphasises how long it takes.
Path to research
Robson, who comes from Newcastle in England, described how she “didn’t follow a classical career path” into research. She left school at the age of 16 and trained as a lab technician in Newcastle University.
Working with a “really prestigious cancer research group”, she studied part-time and landed a PhD position atImperial College London. She went on to work at the University of Ulster and QUB – where she got full professorship –before taking up the position of head of molecular and cellular therapeutics at RCSI.
It was during her time at QUB that the partnership with Almac flourished – it provided R&D funding to her lab as she sought to pioneer the use of the FKBPL protein in the treatment of cancer. “It was a case of being at the right place at the right time,” she said of the collaboration, which continues with her work in Dublin.