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 Madalena Tarsounas

Location: University of Oxford

The challenge

BRCA1 and BRCA2 genes are altered in approximately a quarter of breast and ovarian cancers that run in families. In patients with no family history of breast cancer, the tumour can also sometimes have changes in BRCA genes. Cancer cells with altered BRCA genes are especially sensitive to a type of drug called PARP inhibitors. However, cancer cells can become resistant to this treatment. Finding combinations of drugs that work better together than individually could help overcome this problem by destroying the cancer cells before they can become resistant to one of the treatments.

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

Drug: Chlorambucil

  • A chemotherapy drug in clinical use for certain types of leukaemia and lymphoma - cancers of the white blood cells and lymph nodes.
  • It works by damaging the DNA in a cell and stopping the cell from making a copy of its DNA – a process essential for cells to multiply

The science behind the project

Professor Madalena Tarsounas and her team plan to investigate how effective the combination of talazoparib (a PARP inhibitor drug) and chlorambucil (a chemotherapy drug) is at destroying breast cancer cells with changes in BRCA genes. The researchers are first testing a range of doses, individually and in combination, on a panel of human breast cancer cells with and without BRCA mutations.

Next, they will carefully assess how this treatment works in mice. The researchers aim to achieve the maximum treatment effect with the lowest dose. They are also looking for potential side effects this new combination might have. The researchers hope that by using two drugs at a lower dose will reduce side effects.

They are also investigating how this drug combination works inside cells by using well-understood microscopy and laboratory techniques. Healthy cells will also be used in this step to evaluate if and how these drugs given together may affect them. The researchers are looking for any features cancer cells may have which makes them susceptible to this combination treatment, as well as molecules that can indicate how well the treatment is working.

What difference will this project make?

This project could lead to more effective treatment options for patients whose tumours have changes in BRCA genes. This new double drug combination may be better at destroying cancer cells, have fewer side effects, and be harder for cancer cells to develop resistance to, than a single drug treatment. This project could also lead to the identification of molecular features to be used to monitor how well the treatment is working and know who may benefit most from it.

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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.