PARP inhibitors: killing cancer cells by allowing them to destroy their own DNA

Dr Mariam Orme, post-doctoral researcher in The Institute of Cancer Research's Division of Breast Cancer Research, reflects on the life of former colleague Professor Julian Lewis, and one of the recent breakthroughs that has given men with prostate cancer more time and better quality of life.

Last week, Professor Julian Lewis passed away after a long battle with cancer. Julian ran a research group at Cancer Research UK’s London Research Institute, where I had the privilege of getting to know him a little. Julian touched the lives of all those who knew him, and to the people in his group he was much more than a mentor: he was a valued friend. He was unfailingly kind, patient and respectful in his interactions with other people, and despite his modest nature was a brilliant scientist. He will be missed very much.

Julian was diagnosed with prostate cancer in 2004. The fact that he went on to live for another decade is largely due to the fact that he took part in a clinical trial for a type of drug called PARP inhibitors. These drugs had initially been developed in the 1990s to be used in combination with other anti-cancer therapies; but they turned out to be very toxic when used this way, so they were abandoned. Until 2005, that is, when work done here at the ICR showed that PARP inhibitors could be used alone to kill certain types of cancer cells.

What do the PARP inhibitors do? PARPs are molecules that help to repair damaged DNA. It’s important that damaged DNA gets fixed, because DNA holds the genetic information: it’s the cell’s instruction book. In the presence of PARP inhibitors, the PARPs can’t do their job, but for most cells that’s not a huge problem – they have an alternative way of repairing damaged DNA, using molecules called BRCA1 and BRCA2. Certain tumours, however, have defective BRCA and therefore can’t use this alternative pathway. The team at the ICR realised that hitting BRCA-defective tumours with the PARP inhibitors would be a double-whammy, and the tumour cells would have no way of repairing their DNA efficiently. As a result, they die or at least stop dividing, making PARP inhibitors an effective treatment for these types of tumours.

Thanks to this and other work done here at the ICR, men with prostate cancer are now living for a long time after diagnosis. But each death underscores how important it is to continue our work and develop even better treatment options, so that in future people like Julian can be cured completely. comments powered by Disqus