Field notes from a hepatologist

So, tell us a bit about your work and interests around the diseased liver and how this can drive cancers.

As a clinical hepatologist, the increase in the numbers of patients presenting with hepatocellular carcinoma (HCC) in the UK over the last few years has been concerning. We have long known that most cases of HCC develop in people with chronic liver disease, so we have a clear at-risk population. However, despite a national surveillance programme, most patients with HCC present late, beyond curative treatment.

The biological underpinning of the cancerisation field effect in the chronically diseased liver is not well understood. I am interested in how this field effect is encoded and if detectable, asking if we can use it to diagnose patients earlier – or even to intercept cancer development.

There are lots of worrying stats around the increasing prevalence of diabetes, obesity and other metabolic disorders. As cancer researchers, why should we be worried about this?

Unlike ten years ago, when many HCC patients had underlying viral hepatitis, most HCC patients that I see in clinic now are overweight and many of them have type 2 diabetes, with all the chronic health problems that this entails. This reflects the experience in other clinics across the developed world where the rates of metabolic problems are increasing fast.

This should worry us all as cancer researchers as the cluster of obesity, type 2 diabetes and metabolic dysfunction is a risk factor for breast cancer, colorectal cancer and endometrial cancer, in addition to HCC. Unless we understand why metabolic dysfunction makes development of these diverse cancers more likely, its rising incidence in our population will lead to subsequent rising cancer incidence more generally.

It’s also important clinically as patients who have multiple co-morbidities are less able to cope with curative surgery and more frequently unsuitable for systemic therapies: a good example are anti-angiogenic agents in patients with co-existing heart disease. Therefore, increasing numbers of future patients will not benefit from the outstanding basic cancer research that is on-going now.

What are your thoughts on why metabolic disease can have such far-reaching and devastating consequences?

I think understanding this is key to improving the lives of huge numbers of people in the UK and beyond.

We know this is not just a cancer-related problem: there is a straight-line relationship between economic deprivation and rates of obesity for children at age 10, which means that many of the risk factors for subsequent metabolic dysfunction and cancer risk are hard-wired into our society.

Clearly, we cannot solve these alone, but we can develop our understanding of why these chronic conditions are linked to subsequent cancer development and how we can intervene.

The effect of aging has been key to a lot of your work – and there is real growing interest around aging-based therapies for various conditions. Do you think you can see a path to the clinic for some of your work?

Aging is the key risk factor for the development of cancer, so if we could understand how healthy aging works and why diseases accelerate or subvert this process, we could make an enormous impact on a range of diseases. The area has really exploded recently with various large technology firms getting into aging research.

I was originally fascinated by how diseases could accelerate features of aging at different rates in different tissues. The liver is a prime example of this with multiple features of accelerated senescence during disease of the organ. Targeting of senescence is becoming a viable future therapeutic prospect in multiple clinical trials around the world.

Our recent work has focused on age- and disease-related genetic change in chronic liver disease. We have found accumulation of DNA coding variants related to metabolic dysfunction in patients with liver disease. Many of these variants are functional and dysregulate key metabolic pathways. Over the next few years, we will be working to understand how these variants relate to metabolic dysfunction and liver cancer development.

As a Fellow with CRUK, tell us about what this means for a research career?

I have been very fortunate to have been supported by CRUK over the last 10 years or so with a previous advanced clinician scientist fellowship and now a programme foundation award. These have given me the freedom to develop as a scientist, but also a UK-based community that has been incredibly supportive.

The CRUK fellows’ meetings are a great opportunity to meet clinicians and scientists at similar stages and to develop collaborations that have delivered a lot of the science that I have been involved with over the last few years. Beyond the funding, I have also received great advice and support from Cancer Research Horizons with legal discussions and patent applications, which are languages that I am not fluent in.

The fellowship also comes with important responsibilities. Running Race for Life over the last few years is a reminder of the gratitude that we should all express to our fund-raisers and donors who work so tirelessly to support our science.

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