Professor Nic Jones was recently appointed Chief Scientist of Cancer Research UK. To mark the occasion, we asked him to take part in our ‘expert opinion‘ series of interviews, outlining his view of what’s big in cancer research at the moment.
Professor Jones is also Director of the Manchester Cancer Research Centre, and is a world-leading cell biologist.
Cancer Research UK: For you, what have been the hot topics in cancer research, and specifically lab research, over the past few years?
Nic Jones: I think a number of things have happened over the past 2 to 3 years that are now culminating is some very exciting developments in cancer. As Peter Johnson mentioned in his interview with you, these developments are about ‘personalisation’ of cancer treatment in the future.
Our general knowledge of cancer now is immense compared to what it was even 5 years ago. This has come from very good fundamental work on tumour biology – all that knowledge is now culminating in an understanding of cancer that will allow us to treat it in a very different way than we do right now.
This so-called personalised medicine approach is about developing new drugs that are really targeted against drivers of the growth of particular tumours. And there will be different drivers in one tumour to the next, and one patient to the next.
What’s happened over the past couple years is an explosion of information with respect to the changes that occur in a tumour cell versus a normal cell. Now these changes are vast – there are lots and lots of changes within a tumour cell versus a normal cell. The key is, through an understanding of fundamental biology, being able to identify those changes that are really meaningful in terms of tumour development.
Once we have that information then we can target those changes that are taking place (for example, inhibiting enzymes that might be increased in tumours and driving the tumour development) and really hit tumours at their most vulnerable point.
Cancer Research UK: How is this leading towards ‘personalised’ medicine?
Nic Jones: In essence, that’s the whole basis of personalised medicine – being able to understand what has gone wrong in a particular tumour and why it’s different from one tumour to the next – and then designing and using particular therapeutic approaches that are absolutely specific to those particular changes. We’re not there yet in many cases, but there are examples that are coming through now that really give us confidence that in the next 5 years that this approach will be successful.
What I’m talking about is not necessarily something that has just happened in the past year, but this whole process is accelerating. Technology development is really driving a lot of this. If we think about sequencing the human genome, it can now be done for five thousand US dollars in a few days – that’s immense. Just eight years ago it would take many, many years and hundreds of millions of dollars to sequence a single genome. Now it can be done quickly and cheaply.
That acceleration of technology is going to continue – so I would predict that in 2 years from now we’ll be able to sequence the genome for one thousand dollars, and do it in hours and not weeks. So that kind of technology is really giving us a huge opportunity in terms of getting information – really valuable information – from each particular tumour that is presented within the clinical setting.
The key is being able to interpret the information we get. And that’s not easy. That comes from the fundamental research and the fundamental understanding that we have about tumour biology. It’s really important that this more basic research continues at the same time as we also begin to translate our understanding into potential new treatments for the future.
Cancer Research UK: What specific research or advance is really exciting to you?
Nic Jones: An exciting development over the past couple years is about a concept known as ‘synthetic lethality’. This is where you can ‘hit’ pathways in a tumour cell that are actually pretty normal – they are not deregulated – it’s just that the tumour has become dependent on those pathways, whereas a normal cell isn’t dependent on those pathways.
And now there are tests that are used that can identify these vulnerable points within a tumour cell. The great thing about that is that they are very specific – so if you use a drug to hit a pathway that is only a critical pathway in a tumour cell (versus a normal cell), then you can see that that kind of specificity is really going to lead to more effective and safer drugs in the future.
There are examples of that coming through now – the best example of that is using PARP inhibitors, and Cancer Research UK has been very much involved in the development of these drugs. The results from clinical trials that have appeared over the past couple years are incredibly encouraging in terms of being able to use the drugs against a subset of patients whose tumours have a particular genetic makeup.
The other thing that has excited me is a number of papers that have identified the ‘tumour microenvironment’ as being important in cancer. In the past we’ve really focussed on the tumour itself – identifying changes within the tumour and trying to decipher which ones are important in terms of tumour growth.
What’s become clear is that the tumour sits within a microenvironment. That microenvironment has several different types of cells – normal, healthy cells – that ‘feed’ the tumour. So signalling takes place between this microenvironment and the tumour and vice versa. That microenvironment is crucial in terms of tumour development. And what’s happening now is that ‘signatures’ are being identified within the microenvironment that signify those tumours that are most likely to progress (or not), and also it provides a potential opportunity in terms of therapeutics.
Until now we’ve concentrated very much on the tumour alone in terms of cancer treatment. We can now think about targeting certain signalling pathways that come from the microenvironment. In the future if we hit the microenvironment and hit the tumour, my guess would be that such a combination could be a pretty exciting approach to take.
Cancer Research UK: Which recent advance will have the greatest impact on cancer patients?
Nic Jones: That’s an easier question for clinicians, not basic biologists like myself, but I guess PARP inhibitors – which, as I said, are looking very promising.
But even there, what one begins to realise is that you start getting resistance to the drugs, so tumours come back. There’s a whole other area of very important research that’s taking place which is designed to try to understand drug resistance mechanisms. Ultimately the aim is to try to prevent resistance appearing in the first place, or being able to attack the resistant tumours in the future with a different combination of drugs.
Again, the whole idea of being able to use technology to be able to address those kinds of questions is what’s really exciting. We can ask what changes take place from the primary tumour to a resistant tumour following chemotherapy. And that hopefully will give us information that leads us to understand the events that result in tumour resistance, so the use of newer technologies really is going to have a major impact.
Cancer Research UK: What do you think the next few years of cancer research will bring?
Nic Jones: It’s an incredibly exciting era. I think the understanding we have now of particular cell signalling networks and changes that result in tumours developing is immense. We’ve still got a lot to learn in terms of tumour biology, but the accumulation of knowledge of tumours is really impressive.
The key is how do we use that information – how do we use that understanding to develop better treatments in the future? And so the whole area of translational research is key for us in the future. [Translational research is the process of turning discoveries made in the lab into new treatments.]
I think over the next few years, questions about how we do translational research most effectively and how we bring teams of multidisciplinary scientists and clinicians together to promote that kind of translational agenda are going to be very important – and a challenge.
Cancer Research UK: What other big challenges do you think lie ahead of us?
Nic Jones: The other thing that we need to do over the next few years is use what we call ‘biomarkers’ to help us design clinical trials in the best way in the future. Biomarkers are simply changes in the body that we can recognise using fairly simple tests. We need to be able to use such biomarkers tests to help us to group patients who go into clinical trials in the first place.
Clinical trials these days must have a component associated with them that is all about identification and validation of these biomarkers [validation is making sure that biomarkers can be used reliably and accurately time and time again] – in some cases imaging biomarkers, in other cases blood-borne biomarkers or tissue-based biomarkers.
It’s basically a cultural change more than anything – changing the culture to ensure that the way that we develop new drugs and test new drugs in the future really has this translational element. That means being able to pick the patients in the future who are most likely to respond to a particular therapeutic approach, and test that within a clinical trial setting.
I think the challenge is how do we fund that type of team-based approach? And how do we evaluate that approach in the future?
Cancer Research UK: Finally, what inspired you to work in the cancer field?
Well I just got interested in science in general. I didn’t start off in science saying “I’m going to be a cancer researcher” – I’m just interested in posing questions and getting answers to those questions.
Cancer research is a very exciting field to be in. After I did my graduate work in Edinburgh I went to the States, as many academics do, and ended up in a lab that was working on a type of virus called adenovirus.
We identified a gene called the E1A gene, which turns out to be a very interesting gene that interacts with certain ‘nodes’ within the cell, changing the behaviour of the cell. By identifying what those nodes are, you can then identify what are the really important factors in a normal cell that, when changed, can result in tumours developing. It was just starting off enjoying doing science and, by accident, becoming involved in a scientific area where there was a cancer implication.
Once you’re in the cancer field then I think that you are hooked, because it’s an incredibly interesting field and the importance of it is so immense. It touches everybody – once you’ve been touched by working in cancer research, you’re there for life.
If you enjoyed this interview, then you may also be interested in listening to our recent podcast, where Dr Kat Arney talks with Professor Jones and Professor Peter Johnson about where cancer research is heading.