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Recent Work

PROFESSOR MATT SMALLEY REPORT ON TRIPLE NEGATIVE BREAST CANCER

Our laboratory is studying a form of breast cancer called ‘Triple Negative Breast Cancer’ or TNBC. About 15 out of every 100 breast cancers (15%) are triple negative making it one of the less common forms but it is one of the most aggressive. It tends to spread rapidly (metastasise) in the body and it does not respond to hormone treatment with tamoxifen or the targeted cancer drug trastuzumab (Herceptin).  We have found a gene that seems to be specific to TNBC and when we block its activity in the laboratory it results in TNBC cells growing and moving less. We have also found that this gene comes in two forms, a so-called long and short form. We have found that both forms are important for the growth of TNBC cells but it is the long form which causes the cells to move more, which is what makes them more likely to spread in the body and cause metastasis.

We want to work out the difference between the long and short forms, as we think this will help us identify new approaches for treatment. Thanks to support from Breast Cancer Research Aid, we have now begun to do this. We have isolated the long and short forms from breast cancer cells in such a way that other contents of the cell which were stuck to them were extracted at the same time. The next step was to compare the extracts to find out what was stuck to the long form, but not to the short form (which will hopefully tell us what is controlling cell movement), and what can be found stuck to both forms (which will hopefully tell us what is controlling the growth of the cells). To do this, we worked with colleagues at Bristol University who are expert in a technique called ‘mass spectrometry’. You’ll have seen this if you watch CSI – except on CSI it takes about 2 minutes whereas in reality it took over two weeks! Supported by BCRA, we were able to carry out a mass spectrometry analysis of our extracts.

Although it is still very early days, we think we have successfully identified a strong candidate for the target with which the long form of our gene is interacting to promote cell movement and so make them likely to spread in the body. We still need to prove this with follow-up experiments, but if it turns out to be true, blocking this interaction has the potential to be a new therapeutic approach in TNBC. This study has opened up a whole new area of research for us and it would not have been possible without the support from BCRA. We are extremely grateful

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We are supporting Cardiff University’s European Cancer Stem Cell Research Institute

We are supporting Cardiff University’s European Cancer Stem Cell Research Institute with ground-breaking work they are doing on a finding new therapies for a particularly aggressive form of breast cancer.

The Institute is working on research into a form of breast cancer called ‘triple negative breast cancer’ or TNBC. This tends to be more aggressive and cannot be treated with hormonal therapy or trastuzumab, a common breast cancer treatment.

Researchers at the Institute have found a ‘molecular switch’ called LYN which exists at high levels in TNBC. It is particularly active in TNBC that develops in patients with a defective BRCA1 breast cancer gene.

In the laboratory, the researchers have found that BRCA1-TNBC cancer is very sensitive to blocking LYN and is killed by this approach. More needs to be found out about the physical properties and biology of LYN so that compounds can be developed that could be used in patients.

We are supporting the European Cancer Stem Cell Research Institute by helping to fund studies of this ‘molecular switch’, which will form the basis of the development of new therapies for breast cancer patients.

When discoveries such as this are made, a lot of work needs to go into taking the science from the lab to the bedside. It often involves many small steps that are often expensive. We are helping by giving the Institute flexible support so that they can direct their research down a number of different possible approaches.

 Other research programmes the Institute is working on include looking at how breast cancers develop resistance to new treatments and how to overcome that resistance, as well as more basic studies of breast cancer biology which aim to improve understanding of the cellular and genetic interactions that cause different sorts of breast cancer.

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ICR’s research into liquid biopsy tests

ICR’s research into liquid biopsy tests

The ICR is at the center of ground-breaking research into liquid biopsy tests, which can predict which breast cancer patients will relapse. These new blood tests will mean women can benefit from targeted treatment without the need for uncomfortable biopsies.

We are supporting the ICR by helping to fund this kind of ground-breaking research.

The liquid biopsies use genetic techniques to detect breast cancer DNA in the blood stream. It sho

ws whether a patient is responding to treatment, when a treatment is stopping working, and gives valuable information on the next treatment to try.

The next step for the ICR with this exciting development is to demonstrate that it leads to better outcomes for breast cancer patients. They are currently recruiting patients to a trial that will identify mutations in metastatic breast cancer of individu

al patients and try to match them with specific targeted treatment.

The results of the trial will be available in around two years’ time, and the ICR expects the blood tests to be used in the NHS in the next five years.

This is a very fast-moving area and one that BCRA is excited to be supporting.

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