The Breast Cancer Now Catalyst Programme

To achieve our aim that by 2050 everyone who develops breast cancer will live and be supported to live well, we need to speed up the translation of research in the lab into new and effective treatments for patients. We’re bringing together leading researchers and top pharmaceutical companies to pool ideas and resources and ultimately stop people from dying from breast cancer.

As part of the Breast Cancer Now Catalyst Programme, we have collaborated with leading pharmaceutical company Pfizer to give researchers unprecedented access to a number of Pfizer’s licensed and investigative drugs as well as vital funding for researchers to test these drugs. This allows us to combine the expertise of our researchers with Pfizer’s compounds and deliver new treatments to patients more quickly.

Project details

Researcher: Professor Chris Lord

Location: Institute of Cancer Research, London

The challenge

Drugs called PARP inhibitors are showing promise as an effective targeted treatment for breast cancers with changes in BRCA genes. But some of these cancers don’t respond to PARP inhibitors as well as expected, and others eventually become resistant. This is particularly the case in people who have seen their breast cancer spread to new places around the body. Professor Chris Lord wants to find out more about what causes breast cancer cells to become resistant to PARP inhibitors. This knowledge would allow researchers to identify who will get the most benefit from the drugs, and potentially find ways to make them more effective.

Drug: Talazoparib

  • Belongs to a class of drug called PARP inhibitors
  • Works by blocking the PARP protein so cancers with changes in BRCA genes can’t repair their DNA and die
  • A second generation, more potent PARP inhibitory

The science behind the project

Over time, genetic information or DNA inside a cell can become damaged. All cells have ways to try to fix damaged DNA to survive. But cancer cell’s attempts to fix the DNA can often cause tumours to grow and spread. A protein called PARP is involved in repairing damaged DNA. A group of drugs, called PARP inhibitors, block the action of the PARP protein. Cancers with changes in BRCA genes have been shown to be very susceptible to this treatment.

PARP works by attaching itself to the DNA while the repair process is happening and detaching when it is fixed. PARP inhibitors cause it to become trapped on the broken DNA. In cancer cells, it prevents the DNA from being repaired and causes the cell to die. However, Chris and his team have recently found that these cancer cells can sometimes gain new mutations in their PARP proteins. These mutations mean PARP inhibitor drugs aren’t able to keep PARP trapped on the DNA, and the cancer cells don’t die. In this way, cancer cells become resistant to this treatment.

Chris is now investigating how PARP attaches to the DNA. After treating the cells with a new and highly effective PARP inhibitor drug called talazoparib, he is studying what other parts of the cell are involved in PARP being trapped onto the DNA. He wants to build a bigger picture of how this process works, and how new mutations might cause the PARP inhibitors to stop working. He is using a cutting-edge laboratory technique to create mutated proteins and to see what the effects different mutations have on the DNA repair process.

What difference will this project make?

The information from this study will help us understand why some breast cancers become resistant to PARP inhibitors. It would to ensure doctors are giving this treatment to the patients who will benefit from them most and know when to give other drugs alongside PARP inhibitors to make the treatment more effective. Knowledge gathered through this research can inform future clinical trials to identify and improve treatments for people with breast cancer, giving them the best chance of survival, and ensuring we can control the disease for as long as possible.

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* Pfizer has provided funding and Pfizer compounds for this research study as an Independent Medical Research grant as part of the Breast Cancer Now Catalyst Programme. Pfizer has no other involvement in this research study.