Understanding the role of SF3B1 in breast cancer

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.

Researchers have found that ER positive breast cancer cells that have changes to a protein called SF3B1 grow more aggressively. They are also more likely to become resistant to standard treatments such as hormone therapy. When breast cancer stops responding to treatment, it can spread to other parts of the body and become incurable. We need to understand why breast cancer with changes to SF3B1 doesn’t respond to hormone therapy and find new ways to treat it. It would help to stop more people from dying from this disease.

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

Dr Rachael Natrajan wants to understand the role of the SF3B1 protein in the progression of ER positive breast cancer. In experiments in the lab, Rachael and her team have found that these breast cancer cells are sensitive to a drug called talazoparib. They hope to show that people whose cancer has changes to the protein SF3B1 could benefit from treatment with talazoparib.

The resesearchers will use breast cancer cells grown in the lab with and without changes to the SF3B1 protein and tumour samples donated by patients for their experiment. They will assess whether talazoparib could be an effective treatment for this aggressive type of ER positive breast cancer in combination with standard treatments. They will look at changes to DNA and proteins in breast cancer cells to understand how they respond to this treatment. This will help to determine  what group of breast cancer patients would benefit most from talazoparib. Rachael and her team will also investigate how breast cancer becomes resistant to talazoparib and see if they can find ways to prevent this from happening.

The hope is that by understanding why breast cancer cells with changes to SF3B1 do not respond as well to standard treatments, we could find better ways to treat the disease. This could lead to offering additional treatments, such as talazoparib, to those who need them and stop more people from dying from breast cancer.