PARP inhibitors like olaparib are an exciting new avenue of targeted treatment for breast cancer patients with changes to the BRCA genes. Let’s look at the journey of olaparib from first experiments in the lab until now.

The discovery of PARP inhibitors is the culmination of over a decade of work, which Breast Cancer Now-funded researchers were involved with from the very beginning.

Scientist looking through a microscope

How do PARP inhibitors work?

Olaparib is a member of a group of drugs called PARP inhibitors. 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. Changes and mistakes in the DNA can lead to cancer, so it’s important that our DNA is kept in good condition. And we have an effective DNA repair kit, in the form of the proteins BRCA1 and BRCA2.

However, changes in the BRCA1 or BRCA2 genes, which provide the instructions to make these proteins, put people at increased risk of developing breast and other cancers. The reason is simple – altered BRCA genes mean that a cell could become less able to repair its DNA efficiently. It means further DNA damage can pile up, which can lead to cancer.

Cancer cells with altered BRCA genes are still able to repair DNA, because they have a molecule called PARP. For these cancer cells, PARP isn’t the most effective tool to repair DNA, but it’s pretty much the only one they have. So, these cells are almost completely dependent on PARP to survive.

Based on these observations, researchers came up with a theory that blocking PARP would work well in cancer cells which had altered BRCA genes. Using PARP inhibitors on these cells could leave them 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, London, showed that breast and ovarian cells with an altered BRCA gene were very sensitive to PARP inhibitor drugs like olaparib.

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 in 2017. This trial tested the ideas, that were first proved in the lab by Breast Cancer Now scientists and others, in patients.

In this trial, researchers found that women with secondary breast cancer with changes in either  BRCA1 or BRCA2 gene, who were treated with olaparib, had on average an additional three months before their cancer progressed. They also experienced fewer side effects compared to women who were treated with standard chemotherapy.

In 2021, the OlympiA trial, led by Professor Andrew Tutt from the Institute of Cancer Research, London, showed that people with primary breast cancer could also benefit from olaparib. A one-year course of olaparib added to standard treatment could cut the risk of dying by 32% for some people with HER2 negative primary breast cancer with a change in the BRCA gene.

We hope these groups of patients will be able to access the drugs in the 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 who found that cancers with changes in the BRCA genes are sensitive to PARP inhibitors. He now leads a team at our Research Centre and is continuing to study PARP inhibitors – trying to understand why some cancers might become resistant to them and what we can do to avoid this happening.

Other groups of researchers are already looking at whether other patients could benefit from PARP inhibitors too. Some research suggests that as many as 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 smarter, targeted treatment. These drugs are designed against a specific weakness in cancer cells. It means they are more likely to leave healthy cells unharmed, reducing side effects. 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.

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.

Because of our contribution to the discovery and testing of PARP inhibitors, Breast Cancer Now receives from the Institute of Cancer Research a share of royalties from sales of PARP inhibitor drugs, including olaparib. We re-invest this money to fund world-class research and life-changing support to benefit even more people affected by breast cancer.

It helps us to support hundreds of researchers across the UK and Ireland. Many of them are doing similar lab work to find new breast cancer treatments that could save lives in the future.

But none of this work would be possible without our supporters. 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.'

Watch our video on PARP inhibitors:

More information

Discoveries like this are important steps towards the best possible treatments and support for people affected by the disease.

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