• Professor-Alpha-Yap

Professor Alpha Yap, University of Queensland

What approach do you take with your research on breast cancer? 

My lab focuses on breast cancer because it’s a fundamentally important disease that has huge implications for women’s health.  Where we come from is our understanding of how tissues form and how they hold together.

Importantly, some of the most fundamental and clinically devastating stages of breast cancer occur when the cells within tissues; the cells within the cancer itself start to move and migrate to other parts of the body.

So what we think happens is that the mechanisms that normally control cells and tell them where to stay and where to go become abnormally regulated and we felt we believed that by bringing our knowledge of normal tissue biology we could help to understand how things go wrong in breast cancer, with a view to developing new therapies and new treatments for the condition.

Can you tell us broadly what some of the problems are for people with metastatic breast cancer, what they experience, and some limitations in the current therapies?

One of the most devastating stages of breast cancer is when the cancer spreads, called metastasis. The great danger there is that by spreading, the cancer starts to damage tissues where it shouldn’t be, and the problem is that it’s extraordinarily hard to treat.  By the time it spreads, surgery doesn’t work effectively, radiotherapy is often very toxic, and chemotherapy is limited.  So, we need new ways of treating this late stage of the condition.

How does your research project aim to address some of these problems?

We think about breast cancer, especially metastatic breast cancer, a little bit like a car that’s out of control.  So you could imagine that the abnormal genes that we know drive breast cancer are like a driver that no longer is behaving properly. A lot of the work that is being developed is trying to target the driver. What we’re trying to do is something that’s complementary. The basis of our thinking is if we can mobilise the car then we can make a difference, irrespective of what is happening to the driver. So that’s what we’re trying to do, we’re trying to identify the normal machinery for the cell, that’s being abnormally used by the cancer-related genes and try to see whether we can immobilise them, and if we can effectively help treat the condition.

Our approach is to take cancer cells, compare them with normal cells, look at the mechanisms, the processes that are different that allow cancer cells to move where they shouldn’t move when normal cells don’t, and look particularly at the normal cellular processes that are being abnormally controlled, and to see whether we can control them, if we inhibit those abnormally regulated mechanisms, whether we can stop cancer cells from migrating and behaving abnormally.

Let me give you an example. There is a protein that is found in all our normal cells, that controls whether the cells move or not, and what we’ve found is that in cancer cells, in their early stage, when they move away from the tumour, they need to use this protein to move, and if we block the function of that protein, their movement is stopped.  Now that protein is otherwise absolutely normal.  So what’s happening is that what is usually a normal thing is being used for abnormal purposes, but if we can block it, we can correct, or at least help treat, the underlying abnormality.

What do you think the impact of your research will be for those affected by breast cancer?

What we ultimately hope is that the work we do will lead to treatments that add value, that add to the range of other treatments that are available, so that an individual woman who has the condition, who has cancer, has a range of treatments that may be complementary, a package of treatments that can be tailored to their needs and to their condition.

How important is NBCF funding to your research?

NBCF funding plays an essential role in what we do.  It allows us to do two things that we would have trouble doing otherwise. Through grants like the innovator grants, the Foundation has the courage to support research that may be innovative, that may be early, that may be high risk but potentially high value, and through larger grants, it brings together basic scientists like myself, with translational scientists, with clinicians, so that we can take what we know from discovery all the way, ideally, to the clinic.

What do you think has been the biggest breakthrough in breast cancer research to date?

In some respects, the largest, greatest breakthrough in breast cancer research has come from the identification of the many genes that are abnormally expressed, or abnormally functioning, cause breast cancer.  What this means is that we are now able to provide a more detailed characterisation, a more detailed diagnosis of what’s actually driving the cancer itself.  With a view, at least in part, to developing new treatments that are more focused and targeted exactly against those causal agents.

What’s been your biggest breakthrough as a researcher?

From my point of view, from my personal point of view, from what we do and what my lab does, I think the most exciting thing has been the realisation that the interactions between breast cancer cells and their surrounding tissue play a very important role in controlling the behaviour of the breast cancer cells.  What this means is that not only can targeting the breast cancer cells be potentially useful, but even targeting the normal cells around them may ultimately have some therapeutic benefit.

NBCF’s aspirational goal is zero deaths from breast cancer by 2030.  Do you believe we’re on our way?

I think we definitely are going the right direction to achieve the aim of zero deaths by 2030.  To achieve that though we need to keep discovering, we need to keep working, we need to know more about the disease, and that will help us discover new treatments to complement, to add value, to provide new alternatives for women with the condition.