Janine Erler's Red Hot Women Award

Women are increasingly being recognised for their role in science and scientific research, and this month’s Big Ask is no exception

Dr Janine Erler has recently been named winner of the Pioneer category of the Red Hot Women Awards in recognition of her contribution to hypoxic tumour cell research. Janine is leader of the Hypoxia and Metastasis team at the Institute of Cancer Research’s Section of Cell and Molecular Biology, where she has been studying the effect low oxygen conditions have on cancer and role lysyl oxidase plays in metastasis.

You've just been awarded a Red Hot Women Award – could you tell us what these are and what it was for?

Every year, Red magazine awards women in recognition of their achievements in specific fields. I was the winner of the Pioneer category, based on my research into how cancer spreads (a process called metastasis).

Your work involves observing cancerous cells in low-oxygen conditions – how do you do this and why is it important?

All solid tumours over just a few mm in size contain regions of low oxygen (hypoxia) due to insufficient blood supply and a chaotic tumour vasculature. Oxygen can only diffuse a limited distance such that cells further than about 150 micrometers away from a blood vessel exist in these oxygen-deprived conditions. Cancer cells can survive in these oxygen-deprived conditions and adapt to their environment. The problem with hypoxic tumour cells is that they are resistant to radiotherapy and to many forms of chemotherapy. In addition, they are highly invasive and metastatic. Measurements in cancer patients have shown that patients with low oxygen in their tumours have a higher likelihood of treatment failure, metastasis and decreased survival. Thus, hypoxic tumour cells present a major clinical obstacle.

We try to understand how cancer cells respond to hypoxia in such a way that makes them more aggressive. In order to do this, we utilise a special cell incubator (a Hypoxystation from Don Whitley Scientific) that we keep at 1% oxygen. We incubate cells under these conditions, and measure both changes that occur at the molecular level and changes in their behaviour.

What is lysyl oxidase and what is its role in cancer?

Lysyl oxidase (LOX) is an enzyme that catalyses the crosslinking of collagens and elastin. LOX levels are increased in hypoxia, and we showed that LOX mediates hypoxia-enhanced metastasis. Blocking LOX function prevents cancer cells from invading into neighbouring tissue and from colonising distant organs. We have shown LOX to enhance growth of colon cancer tumours, and the invasion and metastasis of many different cancer types. LOX functions in two ways: first, by changing the physical properties of the tissue in such a way that encourages invasion into neighbouring tissues and entry into the bloodstream; and second, by preparing tissue at distant sites of future metastasis to enhance tumour cell colonisation and metastatic growth.

What are you discovering through this work?

We have uncovered two very promising targets for the development of anti-cancer drugs against metastasis: LOX and family member lysyl oxidase-like 2 (LOXL2). We are also deepening our understanding of how LOX and LOXL2 drive tumour progression. Our work has highlighted the importance of blocking molecules involved in modifying the tissue microenvironment as a method to prevent cancer from spreading.

What's next in this line of research?

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We still have a lot to learn about how LOX and LOXL2 function. They are great drug targets, and it is critical to understand the contexts of when they are important and when they are not, in order to know how best to use targeting agents. These studies include understanding what other molecules they interact with and the signalling networks associated with their functions. I feel a moral obligation to cancer patients to do all I can to better understand these enzymes so that we know how best to treat cancer patients with targeting therapies (context, timing, combination therapies and so on). We are also focused on researching what other molecules are responsible for metastasis driven by hypoxia, with the hope of identifying other good therapeutic targets.