Hunting for the future: How an international collaboration is giving liver cancer researchers hope

For Professor Helen Reeves, the motive to form a wide-scale, ambitious collaboration to tackle liver cancer was simple.

‘’We want to work out why the majority of our patients don’t respond to treatment,” she says.

Deaths from Hepatocellular carcinoma (HCC) incidences in the UK are rising. That, of course, is a problem – but it is the poor prognoses, with five-year survival figures under 25% that means CRUK characterise liver cancer as a cancer of unmet need.

‘’Unfortunately, our patients tend to present at advanced stages, reducing the effectiveness of curative treatments,” says Helen. “Whilst there have been advances in medical treatment, often our patients are not well enough to have them and for those that do, only a minority benefit. Others receive no benefit, or experience side effects that impair the quality of their remaining life.’’

A revolutionary resource

A key element to the project has been the development of the widely accessible HUNTER Biobank.

Liver biopsy carries risks for patients and is often avoided, especially if the diagnosis doesn’t rely on such a procedure.

“From the few patients with early cancers having surgery, we do get some tissues left over,” says Helen. “But these are not representative of patients with advanced cancers having received therapies. While some tissues stored in older biobanks do exist, typically these have not been collected with the right protocols and storage conditions required to support the advances in technologies available now.”

And it’s this advancement in technology, when combined with a biobank like HUNTER, which offers so much promise. Methods for studying tumour microenvironments are dramatically improving how we can non-destructively study gene and protein expression at a single cell level says Derek. “Spatial-omics, as it is called, will provide a deep understanding of biology on tumours that can be expected to lead to new diagnostic, prognostics and therapies for HCC.”

But of course, with new technology and methodology comes a whole raft of new protocols for biobanking.

The HUNTER biobank currently supports over 20 research projects across the UK, Spain, Italy, France and America. It enables efficient tissue collection and data tracking for patients, including their treatment history, personal details and tumour characteristics.

“Together we have recruited almost 800 patients spanning the whole range of liver cancer treatments, from surgery, locoregional therapies, radiotherapy and medical therapies,” Says Helen. “Working in any one centre alone, we couldn’t have done this.’’

Collaboration fuelling excellence

The community nature of HUNTER has not just been important for patient recruitment, it has also brought expertise together. Something which, for liver disease in general, has been vital for UK research says Helen.

“In previous years when liver cancer was not so common in the UK, there was little liver cancer focused research in the UK. In Spain and Italy, liver cancer has been much more common for many years, because of hepatitis C virus infection. So, there was a lot of relevant translational clinical research expertise in Spain and Italy.”

Case in point is Professor Joseph M. Llovet from the research institute IDIBAPS in Barcelona. He is a world leader in HCC research, and his huge profile and experience along with access to datasets and research technologies, is proving to be an enormous asset for the consortium.

“We have benefited so much from his involvement,” says Helen. “And we have now secured further funding from the European Union Mission Cancer to continue our work together.”

“Our Italian colleagues also have been fantastic,” she adds. “They are experts in liver immunology and also the application of serum analyses and single cell transcriptomics.”

Along with connecting leaders, HUNTER promotes a HCC focused PhD training scheme for young researchers – the first of a scheme of this kind in the cancers of unmet need landscape. There are now cohorts of students who have been mentored by previous HUNTER investigators emerging, growing the pool of future leaders of liver cancer research.

Ten students have recently been granted funding – all will be immersed in state-of-the-art techniques and will be forming skills and connections which will allow them to stay in the liver cancer field.

“In my own lab we have a prime example,” says Derek. “Dr Jack Leslie was a postdoctoral scientist working in the HUNTER consortium who has now advanced to a lectureship in cancer immunology at Newcastle. He is establishing his own research team which includes PhD students and technical staff who he will in turn mentor and develop to become a future generation of HCC biologists.”

Hopes for the future

So, is HUNTER the turning point for liver cancer research? It’s certainly an important part of the solution says Helen.

“We now have a wealth of clinical and basic science researchers, at all stages, dedicated to improving outcomes for patients with liver cancer,” she says. “We have created the resource to be able to understand response to therapy and toxicity and are starting to generate biomarker signatures that will transform patient care.”

Since the project began in 2018, HUNTER has had a significant impact within the liver cancer field. Investigators have seen a positive boost in fellowship numbers and programme awards and both Helen and Derek agree that Hunter has raised the profile of all its investigators, with a definite expansion of HCC research across the UK since HUNTER was established.

Helen says: “In total, since being awarded the HUNTER Accelerator, our researchers have leveraged over £30m for UK liver cancer research from funders including CRUK, NIHR, MRC, European Union and Industrial partners.’’

It’s this iterative building – the continual growth of the field – that is so key to pushing research forward.

“Due to the obesity epidemic and continued alcohol misuse plus an ageing population we are anticipating an ongoing increase in the numbers of people who are diagnosed with HCC,” says Derek.

“Treatments are improving but unfortunately HCC remains a very difficult cancer to cure. We must continue to build and develop a cadre of clinician and basic scientists who have a primary focus on uncovering the biology and immunology of HCC and translating these discoveries to innovations in the clinic that improve detection and treatment of HCC.”