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 Aleix Prat

Location: Hospital Clinic Barcelona

The challenge

Oestrogen receptor positive (ER+) breast cancers make up to 80% of all breast cancers. Typically, they are treated with hormone therapies such as tamoxifen. But some cancers may not respond well to treatment or become resistant to these drugs. Researchers now understand that ER+ breast tumours can be further divided into subtypes, some of which may be more likely become resistant to treatment than others. We need to understand which cancers will develop resistance to current treatments, as well as find more suitable therapies when current treatments are no longer effective.

Drug: Palbociclib

  • Blocks the activity of proteins called CDK4 and CDK6, which prevents cells from multiplying
  • Currently in Phase III trials in combination with other drugs for high risk early breast cancer
  • Already used to treat oestrogen receptor positive (ER+) HER2 negative breast cancer that has spread, in combination with hormone (endocrine) therapy

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

Previous research has found a subtype of ER+ breast cancer which also has features associated with other breast cancer types. These tumours don’t respond as well to hormone therapy and people with this subtype of ER+ disease can often have a poorer outcome. There is a need to develop our understanding of this subtype of ER+ cancer so we can successfully treat it.

Palbociclib is a drug currently used to treat people with secondary ER+ breast cancer. For many patients, this drug can be beneficial. But this isn’t always the case when the cancer belongs to this newly-found subtype. Professor Aleix Prat wants to understand why this. He is exploring whether combining palbociclib with other drugs could make these tumours respond better to treatment.

Research has shown that breast cancer cells which make up this subtype of ER+ breast cancer have a lot of damage to their DNA. This means these cancer cells might be susceptible to drugs such as talazoparib, which target DNA repair processes in the cell. Aleix is testing whether this is the case using breast cancer cells grown in the lab. He is investigating whether giving palbociclib and talazoparib together, or in combination with other standard treatments, could be effective at reducing the growth of these tumours. The researchers will then trial this in mice, to see which drug combinations are most effective.

What difference will this project make?

There is an urgent need to develop new treatments for people whose cancers don’t respond well to current therapies. If Aleix and his team find a new treatment combination that is effective at destroying this unique subtype of cancer cells it could be quickly progressed into clinical trials as both drugs are already used in treatment. This new combination could give people with ER+ breast cancer the best possible chance of survival.

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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.