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 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 Claudio Sette

Location: Catholic University of the Sacred Hearth, Italy

The challenge

Many people who develop breast cancer have tumours with features which can be specifically targeted using drugs such as tamoxifen or Herceptin. Triple negative breast cancer currently lacks known targetable molecules, making this form of the disease more difficult to treat. We need to understand more about what’s happening in triple negative breast cancer cells and find new treatment options so we can give people with this type of breast cancer the best possible chance of survival.

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 inhibitor

The science behind the project

In breast cancer cells with altered BRCA genes, a protein called PARP can rescue cancer cells from death, allowing them to survive when they shouldn’t. Blocking PARP with a drug talazoparib causes them to die. PARP inhibitor drugs, such as talazoparib, are currently used in the United States to treat people with advanced breast cancer who also have changes in one of the BRCA genes. But researchers think that these drugs could also benefit some people with triple negative breast cancer who don’t have altered BRCA genes.

Recently it’s been shown that PARP controls a process called ‘splicing regulation’. This process determines which proteins are made in a cell. In triple negative breast cancer cells, splicing regulation might be disrupted, leading to the production of proteins that can make tumours more aggressive. If this theory is correct, PARP inhibitors could be used to treat triple negative breast cancer.

Professor Claudio Sette and his team are studying how PARP contributes to splicing regulation and how this process is disrupted in triple negative breast cancer. They are treating mice with triple negative breast tumours, with the PARP inhibitor talazoparib to assess whether the drug is successful at treating the disease. They are also studying whether any molecular features can help to find out which cancers would be susceptible to PARP inhibitors.

What difference will this project make?

Triple negative breast cancer accounts for around 15% of all breast cancers and currently lacks targeted treatments available for other types of breast cancer. New treatment approaches are urgently needed to treat this form of the disease. This project will help us understand of the role of PARP in triple negative breast cancer cells. This research could find a new use for PARP inhibitors, which are already used to treat some cancers.

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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.