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Developing pioneering treatments

Professor Caroline Dive CBE and her team are working side by side with The Christie, developing ‘liquid biopsies’ to hunt cancer cells that have broken free from tumours and are circulating in the bloodstream. Here she tells us why her anticipated three year stay in Manchester has turned into 19 and counting!

Manchester and I have a very long history. I only ever planned to stay for three years, it wasn’t ever meant to be forever. I came here in 1990 and I’ve seen the place just go from strength to strength. As time progressed I rapidly saw that this was a place where basic and clinical research can interface; there are very few places where this could happen so effectively, so I’ve never left.

My research is focused on lung cancer, the world’s biggest cancer killer, and I’m developing blood tests to capture cancer cells that can help researchers understand how lung cancer changes as it grows and spreads, and how it can become resistant to treatment. This will open up opportunities to develop new therapies to treat this deadly disease more effectively.

“Thanks to long-term Cancer Research UK funding, I’ve been able to build something, an infrastructure that will allow us to undertake long-term biomarker research – within our biomarker centre.”

There has been a revolution in the basic understanding of cancers and how we can personalise treatment. We have entered an era of personalised medicine, where information about the molecular makeup of an individual patient’s cancer is used to tailor their treatment. Understanding a patient’s cancer usually involves taking a tumour biopsy. This doesn’t always paint a full picture of the disease though, especially if the disease has spread through the body. On top of that, taking repeated biopsies can be difficult and very invasive for patients.

A research first

My research group (within the  CRUK Manchester Institute) has a strong interest in lung cancer research, particularly  small cell lung cancer (SCLC),  the most aggressive type that kills 220,000 people every year. Tumour biopsies are scarce in SCLC  so back in 2014, we showed that circulating tumour cells (CTCs) can be taken from the blood samples of patients with small cell lung cancer and grown to form tumours, just like the patient’s, in mice. This was the first time lung tumours had been grown away from the patient in this way, with only a 10ml sample of blood needed from the patient rather than an invasive lung biopsy. We call these new models, patient CTC Derived eXplant models (CDX for short) that mimic the donor patients’ tumour pathology and response to chemotherapy. Our growing panel of SCLC CDX models are enabling our investigations into the biology of SCLC and its mechanisms for dissemination. These models also facilitate testing of new therapies and biomarker development, leading to early clinical trials in patients with urgent medical need. This is helping us to understand the biology of addressing small cell lung cancer.

At the start of my career, most clinical trials were run without informative biomarkers, but today we are seeing tumour biology being better understood and the biomarkers that come from this understanding are driving the design of clinical trials. Our new Manchester Centre for Cancer Biomarker Sciences is at the heart of this.

 

Biomarker research doesn’t happen overnight, it takes time and thanks to long term Cancer Research UK funding, I’ve been able to build something, an infrastructure and critical mass of motivated staff,  that will allow us to undertake long term biomarker research – within our biomarker centre.

Meeting need

Aligned to these incredible facilities and the basic and clinical science is the huge unmet need within Manchester’s population,and a culture which says let’s get together and do this, let’s bring together our lab and clinic at the interface. These multidisciplinary teams respect each other.

Manchester’s reputation for cancer research just wasn’t here when I arrived. It’s been such a pleasure to be part of the journey where we are now becoming acknowledged as international leaders in cancer research.

Manchester is hugely ambitious but with that comes the risk of trying to do too much, of spreading ourselves too thinly. We’re getting so many requests for collaborations that it’s not a matter of what to do next, but what not to do. Personally there aren’t enough hours in the day but we’re developing an amazing team and with that capacity, anything is possible.

We’re in an exciting expansion phase and in the future I hope that personalised medicine will become more and more commonplace in the clinic and that we will be using liquid biopsies (blood tests) routinely to inform a patient’s treatment. For me, the biggest challenge that I think we’re facing in lung cancer research is the lack of early detection biomarkers and we are trying to develop tests to pick up early cancer associated molecules shed into the in the bloodstream at low levels. Ultimately I’d like to see the development of very sensitive tests and people giving blood samples within their communities so that cancers could be diagnosed earlier with better chance of effective treatment, especially those who are hard to reach but are at high risk.

Global ambition

Long term, I hope that we’ll become the best biomarker centre in the world. There are of course things we need to do make this happen: we need to expand and diversify, but it’s all possible. Manchester has the potential to make the difference on a grand scale.  It is a jigsaw puzzle which has all the pieces and we’re rapidly putting them together.

Manchester has enabled me to have a fantastically enjoyable and challenging career and our future research plans are ambitious and exciting, bringing the science and the clinic ever closer together.
I’ve got wonderful colleagues who share a passion for clinical and translational research. We can express ourselves scientifically here because the culture is conducive to answering all those scientific questions that we have.

Manchester’s pioneering development in biomarkers is world leading and is helping to understand the biology of addressing small cell lung cancer.