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 Simak Ali, Dr Lesley-Ann Martin

Location: Imperial College London

The challenge

Palbociclib can be an effective treatment for controlling oestrogen receptor positive (ER+) breast cancers that have spread. But over time tumours can become resistant to this treatment. It means the drug stops working and cancers continue to grow and spread. To make sure we can continue controlling the tumours that have spread, we need to find new drugs that can continue to work after breast cancer cells have developed resistance.

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

The science behind the project

The life cycle of a cell is in part controlled by interactions between proteins called CDKs. The breakdown of this process is a universal characteristic of cancer. Most tumours have abnormalities in the function of CDKs. This is particularly common in oestrogen receptor positive (ER+) breast cancer, where oestrogen works with CDK4 and CDK6 proteins to promote cancer growth. Palbociclib is a drug used to treat people with ER+ secondary breast cancer. It works by blocking CDK4 and CDK6 proteins, reducing the growth of cancer cells and controlling the tumour. However, cancer cells can eventually become resistant to palbociclib. Professor Simak Ali, Dr Lesley-Ann Martin and their teams are investigating why.

Simak and Lesley-Ann want to explore how the CDKs work together and what role they play in cancer’s resistance to palbociclib. They are investigating whether CDKs are able to replace each other, and therefore allow the cancer cell to continue to grow even when being treated with palbociclib. One CDK in particular - CDK7 - is thought of as a ‘master regulator’ and is needed to turn on other CDKs. The researchers are investigating whether blocking CDK7 can stop the growth of tumours, and therefore provide a new treatment option for people if palbociclib stops working.

What difference will this project make?

The findings from this project will help to grow our knowledge of why and how cancer cells become resistant to drugs like palbociclib. This will mean that in the future we can develop ways to monitor a patient’s tumour to tell if it is likely to become resistant, as well as finding new ways to treat these patients to ensure that their breast cancer is being controlled. Several drugs that block CDK7 are already being developed, so this project has the potential to lead to a brand new treatment for palbociclib-resistant breast cancer.

Make a donation to support our research



* 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.