PARP inhibitors
In June 2009, scientists at The Royal Marsden and The Institute of Cancer Research (ICR) published pioneering results from a Phase I clinical trial of PARP inhibitors in the prestigious New England Journal of Medicine. This work has been cited as a classic example of bench to bedside translational research that has yielded a personalised treatment with a completely new class of anti-cancer treatment.
In the trial, patients with inherited forms of advanced breast, ovarian and prostate cancers – caused by mutations in the BRCA1 and BRCA2 genes – were treated with the new drug olaparib (a PARP inhibitor).
Background
Scientists at the ICR had originally discovered the BRCA2 gene over a decade ago. They also worked out that it increased the risk of developing cancer because the faulty gene impaired the cancer cell’s ability to repair DNA.
They subsequently established that these cancers were especially sensitive to a new class of drugs called PARP inhibitors, and led the first trial in the world to test this concept in patients with inherited forms of cancer due to BRCA1 and BRCA2 mutations.
Trial results
The results of this early clinical trial exceeded expectations, and despite having previously received many standard therapies the treatment was effective in more than half of the patients. Indeed, one of the first patients to be given the treatment is still in remission after two years. Patients experienced very few side effects, and some reported the treatment was significantly easier than chemotherapy.
The Phase 1 trial was led by Dr Johann de Bono at The Royal Marsden, and these positive results have confirmed that olaparib should be taken into larger patient trials. This is one of the first successful examples of a new type of personalised treatment in which the treatment works by targeting a specific molecular defect within the cancer, and where a molecular diagnostic test can identify the patients for whom this would be the most effective treatment.