PUBLISHED ON: 30 June 2021

Our scientists are studying what role specific genes and proteins play in breast cancer. Proteins are essential building blocks of the machinery in our bodies, and genes provide the instructions on how to make them. This means that changes to genes can change how proteins work. In this blog, we explore some of the genes and proteins our scientists study and how this knowledge can lead to new treatments.

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BRCA

BRCA1 and BRCA2 genes are the most common inherited altered genes that increase the risk of breast cancer. These genes provide instructions for cells to make the BRCA1 and BRCA2 proteins that help repair damaged DNA. When these proteins don’t work properly, it can lead to cancer, including breast cancer.

Understanding the role of BRCA proteins in breast cancer led to the discovery of a new type of drugs, called PARP inhibitors. PARP inhibitors block a protein called PARP. Cancer cells with changes in BRCA genes rely on the PARP protein to repair damaged DNA and survive. It makes them very susceptible to PARP inhibitors.

Research carried out by Breast Cancer Now researchers contributed to PARP inhibitors becoming a breast cancer treatment. They are now used to treat people with HER2 negative, secondary breast cancer and an altered BRCA gene. Recent research has shown that PARP inhibitors can help prevent breast cancer coming back and could also be used to treat primary breast cancer.

PER3 and NOCT

Researchers from the University of Leicester supported by Breast Cancer Now, have found that people with particular variations in two genes, called PER3 and NOCT, were at greater risk of side effects when receiving radiotherapy treatment in the morning.

The two genes help control the body’s internal clock. Variations in these genes mean that some people may benefit from receiving radiotherapy treatment in the afternoon. Scientists found this by analysing the genetic profile of 879 breast cancer patients undergoing radiotherapy treatment.

Larger studies are now needed to replicate these findings. This kind of genetic analysis could help healthcare professionsals personalise radiotherapy so that side effects can be reduced. It could be done by identifying people who would benefit from being treated in the afternoon and those who could be treated at any time.

NUP98

Our researchers at Queen’s University Belfast found that a high level of the protein NUP98 in triple negative breast tumours is linked to a poorer response to anthracycline-based chemotherapy and worse survival outcomes.

Anthracyclines, such as epirubicin and doxorubicin, are a group of chemotherapy drugs that are commonly used to treat triple negative breast cancer. They can be highly effective for some people with the disease but may not work for others.

Researchers hope this knowledge could lead to a simple test for NUP98 levels. It would help to find patients who are unlikely to benefit from anthracycline chemotherapy and should be given a different treatment.

Interleukin beta

Our researchers at the University of Manchester have found that interleukin 1-beta, a protein made and released by the bone marrow, plays a role in the spread of breast cancer to the bone. It encourages breast cancer cells to settle and form tumours when they reach the bone.

Importantly, there already are drugs that block the action of interleukin 1-beta, such as some arthritis drugs. In experiments in mice, researchers found that these drugs can block the way in which interleukin 1-beta encourages the growth of secondary breast cancer in the bone. It means in the future some arthritis drugs could be used to treat breast cancer and prevent the disease from spreading to the bone. We already know that these treatments are safe, which means that they could reach breast cancer patients faster. Researchers hope that clinical trials to test these drugs to treat breast cancer could be ready to start in a couple of years.

Endosialin

Endosialin is a protein that is found on the surface of cells called pericytes. It is thought to be involved in helping breast cancer spread around the body.

Pericytes are large, spider-like cells that sit on the outside of blood vessels and support their growth and function. Breast tumours need a constant blood supply. The growth of blood vessels nearby helps them survive. As well as providing breast cancer cells with the oxygen and nutrients they need, blood vessels also provide an escape route for them to move around the body.

To understand endosialin more, our researchers from the Breast Cancer Now Toby Robins Research Centre at The Institute of Cancer Research, London grew pericytes and cells that form blood vessels in layers to replicate how it works in the body. They found that when endosialin wasn’t present on pericytes, breast cancer cells were less able to migrate through these layers. They are now working to fully understand how endosalin helps breast cancer cells move into blood vessels. The researchers believe that it may be possible to stop cancer fom spreading by targeting endosialin with new drugs, which they will explore in future studies.

Folate receptor alpha

Researchers, at the Breast Cancer Research Unit at King’s College London, found that highly aggressive triple negative tumours, including those resistant to chemotherapy, make high levels of a protein called folate receptor alpha (FRα). They also found that antibody immunotherapies targeting FRα reduced the growth of triple negative tumours in mice, helping the immune system to target and destroy cancer cells.

Triple negative breast cancer currently lacks targeted treatments. The researchers hope that these immunotherapies can be further developed and tested in clinical trials. They could help provide a new much-needed treatment for triple negative breast cancer.

Research can bring vital knowledge of the roles that different genes and proteins play in breast cancer and give us hope for the future. Understanding how genes and proteins are involved in breast cancer could lead to new treatments and new ways to find out who would most benefit from these treatments. Great progress has already been made, but there is a great deal more to learn if we are to achieve our goal that by 2050 everyone diagnosed with breast cancer lives and is supported to live well.

 

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