A recent clinical trial tested a drug called olaparib (Lynparza) for women with secondary breast cancer who carried changes in either their BRCA1 or BRCA2 genes. The results from the OlympiAD trial demonstrated that, in comparison with standard chemotherapy, women treated with olaparib had, on average, an additional three months before their cancer progressed and experienced fewer side-effects.
At Breast Cancer Now we’re delighted to hear this news, primarily because this suggests that olaparib could potentially become a new treatment option for women living with BRCA-mutated secondary breast cancer – but also because these results are the culmination of over a decade of work, which Breast Cancer Now-funded researchers were involved with from the beginning.
What is olaparib?
Olaparib is a member of a group of drugs called PARP inhibitors. As the name suggests, these drugs block a molecule called PARP, which has a role in repairing DNA.
DNA is the instruction manual that tells our cells what to do and how to behave. Faults and mistakes in the DNA code can lead to cancer, so it’s important that our DNA is kept in tip top condition. And we have an effective DNA repair kit, in the form of the proteins BRCA1 and BRCA2.
However, faults in the BRCA1 or BRCA2 genes (which provide the instructions to make these proteins) put women and men at increased risk of developing breast and other cancers. The reason is simple – BRCA gene faults mean that a cell could become less able to repair its DNA efficiently, meaning further DNA damage can pile up, which can lead to cells becoming cancerous.
To be more exact, cancer cells that carry BRCA mutations aren’t completely unable to repair DNA, because they still have this molecule called PARP. For these BRCA-mutated cancer cells, PARP isn’t the most effective tool to repair DNA, but it’s pretty much the only one they have – and so these cells are almost completely dependent on PARP to survive.
Therefore, the theory was, in cancer cells which had BRCA mutations, blocking PARP with PARP inhibitors would render cancer cells unable to repair their DNA – causing them to die.
Proving the power of PARP inhibitors
In a landmark research paper published in 2005, a Breast Cancer Now-funded team helped prove this theory right. The team, led by Professor Alan Ashworth, based at the Breast Cancer Now Toby Robins Research Centre at the Institute of Cancer Research in London, showed that BRCA-mutated breast and ovarian cells were very sensitive to PARP inhibitor drugs like olaparib. You can read more about the discovery in this article.
Fast forward to the present day, and all this work eventually led to the OlympiAD trial, led by Dr Mark Robson from Memorial Sloan Kettering Cancer Center in the USA, which announced its first results at the 2017 Annual Meeting of the American Society of Clinical Oncology, and in a research paper in the prestigious New England Journal of Medicine. This trial tested in patients the ideas that were first proved in the lab by Breast Cancer Now scientists and others.
These drugs, which are already used to treat patients with advanced ovarian cancer who carry BRCA mutations, may provide a much-needed new treatment option for secondary breast cancer patients with BRCA mutations who have either triple negative or hormone-receptor positive forms of the disease. We hope these groups of patients will be able to access the drugs in future.
The work continues
But the story of PARP inhibitors is not finished, and researchers funded by Breast Cancer Now continue to play a leading role.
Professor Christopher Lord was part of the team described earlier who found that BRCA-mutated breast cancers are sensitive to PARP inhibitors. He now leads a team at the Breast Cancer Now Research Centre and is continuing to study PARP inhibitors – trying to pre-emptively understand why some cancers might become resistant to them and what we can do to avoid this happening.
Professor Andrew Tutt was another member of that 2005 team, and is now the Director of the Breast Cancer Now Research Centre and our Research Unit at King’s College London. He is leading an international clinical trial called OlympiA, which is studying whether treating women with BRCA-mutated primary breast cancer with olaparib will help reduce their risk of breast cancer coming back.
Other groups of researchers are already looking at whether other patients could benefit from PARP inhibitors. For example, results published in March 2017 suggested that as many as 20%, or 1 in 5, women with breast cancer could potentially benefit from these drugs.
Why research matters
PARP inhibitors like olaparib are a great example of a ‘targeted treatment’ – drugs designed to tackle a particular type of breast cancer by exploiting a specific weakness in these cells, whilst hopefully leaving normal healthy cells relatively unscathed.
Our hope is that by developing more targeted treatments, we can ensure that everyone with breast cancer gets treatment tailored to them, giving them the best possible chance of survival and quality of life.
But developing smarter treatments doesn’t happen overnight. While the results from clinical trials are what patients and doctors rightly look forward to, underpinning these trials are years of work in the lab, to gain the knowledge needed to develop these new treatments.
So when it comes to PARP inhibitors, it is fair to say we wouldn’t be where we are today without the lab research funded by Breast Cancer Now.
Breast Cancer Now supports hundreds of researchers across the UK and Ireland, many of whom are doing similar lab work to identify new targets for breast cancer treatments, which in time will find new ways to help people diagnosed with breast cancer live.
But none of this work would be possible without our supporters – they work incredibly hard to raise money to power all the research, and they are as much responsible for discoveries like these.
As Professor Christopher Lord puts it:
“As much as we as scientists have this sense of achievement about what’s happened with PARP inhibitors, everybody who raised even a penny for Breast Cancer Now should feel that achievement as well.”
The coronavirus pandemic has put a lot of our lab-based research on hold. But we don’t want to lose momentum or to let progress stall. We need your support, now more than ever, so that our researchers can make up for lost time.
Watch our video on PARP inhibitors: