07 Sep 2015

Cracking radiotherapy resistance: our PhD scientist makes new breakthrough

Following the announcement of our five new PhD scientists last week, Sophie Lutter finds out how one doctorate researcher used their grant from Prostate Cancer UK to make new advances in overcoming radiotherapy resistance in cancer cells.

Since we’ve just announced our five new signings to Men United, this seems like the perfect time to celebrate the recent success of the recently-qualified Dr Conor Hanna. Because Conor had his PhD studentship funded by the Movember Foundation and joined the Men United team in October 2011 to work with Professors Kevin Prise and Richard Kennedy at Queen’s University Belfast.

Not only has Conor passed his PhD this year – which some might say is enough of a reason to celebrate – but he's also had his work published in Cancer Research, the journal of the American Association of Cancer Research.

Again, some might think that this alone is enough of a reason to celebrate (and they’d be right). But for us, it isn’t just the publication that’s exciting but the research itself.

Targeting the PTEN gene

Conor set out to understand why radiotherapy is less likely to be successful in men who have a mutation in a gene called PTEN, and what we could do about it. PTEN is what’s known as a tumour-suppressor gene, and – as the name suggests – it usually works to put the brakes on cell division so that cells don’t grow too fast and become cancerous.

Conor and his colleagues knew that radiotherapy on its own isn’t enough to kill prostate cancer cells that don’t have a working PTEN gene, so they went on the hunt for something that is.

Cells – including cancer cells – can survive with a certain amount of damaged DNA, but the cell will die if the damage gets too bad. Conor and his colleagues wondered whether stopping PTEN deficient cells from repairing their damaged DNA might just push them over the edge. This turned out to be the case.

Proven to work on tumours in mice

The next step was to see whether this might hold true in actual tumours, rather than just cancer cells grown in isolation. They looked at tumours in mice whose PTEN gene didn’t work, and compared the size of the tumours between mice that were and weren’t treated with a drug to block DNA damage repair. They found that the tumours grew far more slowly in the mice that were treated with the DNA damage repair blocker, showing that this treatment could work in whole tumours as well as in cells grown in the lab.

Finally, to round the story off nicely, Conor found that using the DNA damage repair blocker in cells without PTEN made them more sensitive to radiation, suggesting that combining these two treatment options could help bring down the number of men whose prostate cancers are resistant to radiotherapy.

Conor may now have finished his PhD but the story of his research is far from over. His lab mates will now pick up the baton and continue this work as part of the Belfast-Manchester Movember Centre of Excellence. They plan to work with the company who developed the DNA damage repair-blocking drug to see if they can use a newer version of it to continue their research into a clinical trial.