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: Dr Violeta Serra

Location: Vall d'Hebron Institute of Oncology

The challenge

Up to 80% of breast cancers have high levels of the oestrogen receptor. Generally, this form of breast cancer, also called oestrogen receptor positive (ER+), can be treated successfully with hormone therapies which disrupt the action of the hormone oestrogen. However, some cancers can become resistant to hormone therapies, which may give the disease a chance to spread. When breast cancer spreads, although treatable, it can’t be cured. We need to develop treatments that keep the disease under control, giving people with secondary breast cancer the best possible quality of life.

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: Gedatolisib

  • Gedatolisib is a drug that blocks two proteins, PI3K and mTOR, which can help breast cancer cells to multiply uncontrollably
  • Gedatolisib is currently in early stage clinical trials to treat oestrogen receptor positive (ER+) breast cancer
  • Many other drugs that block PI3K are in various stages of development for breast and other cancer types 

The science behind the project

Many breast cancers with high levels of the oestrogen receptor also make a protein, called the androgen receptor. There is growing evidence that these two receptors can influence each other, although it’s not fully understood how. Dr Violeta Serra and her team want to investigate their relationship further. They are testing whether combining drugs to use this relationship, could provide a new treatment for secondary oestrogen positive breast cancer.

RAD140 is a newly developed drug which turns on the androgen receptor. It can influence how the oestrogen receptor works and in previous studies, this has led to a decrease in cancer’s ability to grow. Violeta and her team also think that treating people with RAD140 could bring additional positive side-effects such as an increase in muscle mass.

Using cancer cells donated by people with secondary breast cancer, Violeta and her team are studying what happens inside these cells when the androgen receptor is turned on. She is testing whether RAD140 could be a potential new way to treat oestrogen receptor positive breast cancers. The researchers are studying whether RAD140 can be combined with drugs that target common mutations found in secondary oestrogen receptor positive breast cancer, such as palbociclib and gedatolisib. The team aims to uncover which tumours might respond to the combination of one of these drugs and RAD140. Violeta is testing this in mice with tumours that have been derived from samples donated by people with secondary breast cancer. Researchers will see whether this combination is successful in decreasing their growth.

What difference will this project make?

This project will tell us more about the role of the androgen receptor in breast cancer cells. The results from this study could provide new treatment options for people with secondary oestrogen receptor positive breast cancer. Violeta also thinks that targeting the androgen receptor could be a successful way to treat early oestrogen receptor positive breast cancer.  

 

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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.