From bedside to bench and back again
Professor Gordon Jayson is a clinician researcher whose work offers the complete pipeline of research. Focusing on ovarian cancer and drug development, here he tells us why Manchester’s ability to run multiple novel clinical trials is the key to us becoming recognised as international cancer research leaders.
My career has involved developing new treatments for cancer and I’ve been able to do this in Manchester because the infrastructure and facilities naturally lend themselves to this. Every day I work on a clinical campus which includes The Christie, the University and the research facilities.
Anyone who works with me will testify that my day is spent crossing the road, back and forth, commuting between my patients in the hospital and working in the laboratory. How many people can enjoy a commute so short yet so productive and rewarding? I’m literally traversing two worlds, the clinical and the basic science, many times a day. It’s amazing and something I try not to take for granted.
“My hope for Manchester’s cancer research community is that we come together to develop a truly world-leading clinical trials infrastructure that makes us the envy of every other cancer centre.”
The partnership between the University, St Mary’s Hospital and The Christie provides a unique environment in which to manage our patients. In 2016, we published a paper showing that patients managed by us and other similarly large, research-active cancer centres resulted in international levels of survival, which were 42% better than the UK national average. It’s within this unique group of experts that we have developed The University of Manchester ovarian cancer group, which brings together experts in gynaecological cancer surgery, medical oncology and laboratory science to lead research on the disease.
My research looks at how we can develop new treatments for cancer, particularly ovarian cancer, by focusing primarily on drugs that can block blood vessels forming so that tumours are then starved of oxygen and nutrients.
Angiogenesis, the formation of new blood vessels, has been validated as a target in ovarian cancer in patients with recently diagnosed ovarian cancer, as well as in patients with chemoresistant disease. However, the drugs that target angiogenesis have a range of negative side effects and they are expensive so there is an imperative to identify patients who benefit from them and those that won’t. This research is really important as it will allow us to stop treating patients who won’t benefit from the treatment from suffering any unnecessary side effects, whilst also reducing the costs of unnecessary treatment for the NHS.
Our drive to personalise treatment has led us to delivering a number of biomarker studies, the first of which was an international translational research programme within the ovarian cancer clinical trial (MRC ICON7) which saw our data identifying the first vascular response biomarker, the concentration of plasma Tie2.
The best way of validating this finding was to conduct a similar study in another disease. Therefore, in an entirely Manchester-based biomarker study we studied blood and imaging biomarkers in patients with metastatic colorectal cancer to confirm that the concentration of plasma Tie2 is the first, generic, tumour vascular response biomarker for vascular endothelial growth factor (VEGF) inhibitors. Having completed this work we now propose to apply the test in the NHS and if validated, this test would be used to determine when, and for how long, patients benefit from VEGF inhibitors.
One of the most exciting findings that emerged from this research was that in ovarian and colorectal cancer, we could improve the modelling of progressive disease if biomarker data from the epithelial compartment were studied alongside the biomarker data from the vascular tissue compartment.
Taken in conjunction with numerous clinical trials, which have shown that targeting the tumour vasculature postpones recurrence of cancer, the inference of these findings is that the vasculature should be treated at each recurrence of angiosensitive cancers (e.g. colorectal and ovarian) using Tie2 to guide therapy.
Accepting this novel concept, we are now proposing trials that will treat and re-treat these tissue compartments at each recurrence; the multi-tissue compartment model of cancer treatment. Extrapolating these concepts further, if we accept that we should target tumour epithelium and vasculature, then it remains possible that other tumour compartments e.g. the immune system, should also be targeted at each recurrence.
I think it’s safe to say that this research, carried out by teams in Manchester, has made a significant contribution to how we treat ovarian cancer, in whom and when. This ability to run clinical trials and to take our learning from these into the hospital is making a huge and positive difference to thousands of women’s lives. We’re enabling them to live longer and cancer-free lives, and protecting others from unnecessary treatment.
Building a clinical trials infrastructure
My hope for Manchester’s cancer research community is that we come together to develop a truly world-leading clinical trials infrastructure that makes us the envy of every other cancer centre. We have opportunities here that many other centres don’t. We have the access to patients and the willingness of the clinical, academic and basic science partners to work together.
The key is to expand so that clinical researchers like me can run more trials which result in increased knowledge about how we can better improve patient care and treatment. Not just in ovarian but in all cancers. This is how we’ll run the trials that change patient management and how we’ll become world leading.
Manchester is an incredible centre to carry out cancer research and I have seen a fantastic transformation of the Manchester Cancer Research Centre into a leading international focus of research and high quality cancer care.
Manchester’s ability to run multiple novel clinical trials is driving international recognition for the City’s cancer research community.