Highlighting ‘basic research’ for cancer treatment

Professor Paul Workman, Chief Executive of The Institute of Cancer Research, London outlines why ‘basic research’ is critical for understanding and treating cancer…

Cancer research often makes the biggest headlines at the point when it begins to benefit patients.

The Institute of Cancer Research (ICR), London, is very well known for this kind of ‘translational research’ – where we move new research ideas and approaches out of the laboratory and into the clinic for the first time. This in turn leads on to later-stage clinical research, where the benefit for people with cancer is eventually demonstrated in larger trials. But in order to come up with innovative approaches to cancer treatment, we need first to have made exciting new scientific discoveries that illuminate our understanding of the molecular basis of cancer.

First understand – then translate

This earlier stage of research goes by a number of names – basic research, fundamental research, discovery research, exploratory research, or sometimes ‘pure’ or ‘blue skies’ research.

Basic research generates and tests new ideas, principles and theories about the world. The research findings can often be surprising and unexpected. Fundamental cancer research is crucial because it leads to incremental and sometimes spectacular advances in our understanding of the molecular basis of malignant disease – explaining how tumours grow, invade, spread and evolve.

Here at the ICR, we have always believed that to defeat cancer it’s essential that we carry out basic research on this disease in tandem with translational and clinical research. What’s more, we believe that all of our research needs to be integrated closely with the care of cancer patients.

This is why the ICR’s partnership with The Royal Marsden hospital is so important. By embedding our basic, translational and clinical research with the care of cancer patients we can ensure not only that the earlier-stage research is connected and channelled to clinical need, but also that we achieve the most rapid possible progression of new ideas and treatments into routine clinical practice.

Basic, translational and clinical research at the ICR

Proof of the importance of basic cancer research discoveries can be found in the ICR’s history.

In the early 1960s, here at the ICR we provided the first conclusive evidence that the basic cause of cancer is damage to our DNA. It was a discovery that changed scientific opinion dramatically – since up until that point, proteins had widely been thought to be the site of action for cancer-causing chemicals. This paradigm shift paved the way for the ICR and others to discover, at first one by one, the particular genes that undergo cancer-causing changes in their DNA code, and ultimately to understand their mechanisms of action – such as many genes that increase the risk of cancers that run in families.

It was an ICR team that discovered the BRCA2 gene – mutations in which dramatically increase the risk of developing breast cancer, and of several other cancer types.

As a result, families with a history of breast, ovarian and prostate cancer can now be assessed for future risk, and where necessary offered preventative measures or close monitoring. And the ICR’s Professor Alan Ashworth and colleagues then built on the discovery of the gene by devising a brand new approach for treating women with inherited BRCA mutations – by using a new type of drugs called PARP inhibitors that specifically kill cancer cells with these BRCA defects.

We also played a major role in uncovering the role played by mutations in the BRAF gene in cancers such as malignant melanoma. It was that discovery which allowed others to make drugs to block faulty versions of BRAF, giving us the new cancer drugs vemurafenib and dabrafenib. These were the first drugs in decades to be approved for lethal melanoma, and have both been recommended for use on the NHS by NICE.

Other research originating at the ICR has produced new panRAF drugs that could be even more effective. It was researchers at the ICR too who first made the basic discovery that explained the function of a then poorly understood organ called the thymus – and its critical role in the immune system. That discovery underpinned all of modern immunology, and paved the way for the breakthrough immunotherapies which are now, 50 years later, producing such powerful anti-cancer effects in cancer patients.

The ICR’s basic research has also played a leading role in meeting what I believe to be the biggest challenge we face in treating cancer today – the genetic diversity of tumours, and their ability to become drug resistant.

The problem is that cancers evolve and develop resistance to treatment in a kind of Darwinian survival of the fittest – which I like to describe as the ‘survival of the nastiest’.

One of the ICR’s leading scientists, Professor Mel Greaves, was a pioneer in what is known as ‘clonal evolution’ in cancer. This basic research provided a fundamentally new insight that changes the way we think about how cancers develop and behave, and is now beginning to shape the way we design and implement new treatments.

Research culture

From the beginning of my career, I have always sought to bridge basic and applied research and I find the interface between the two – and especially multidisciplinary team science – exciting and rewarding.

As Chief Executive and President of the ICR, a high priority for me is to foster an organisational culture which allows basic cancer research to thrive alongside the translational and clinical research that is essential to our mission.

 It’s true that basic research can be unpredictable – in the discoveries made, and in where they lead. That’s in the nature of this kind of research. We can though make sure that the basic cancer research we do is integrated very effectively with the more applied work we carry out at the ICR.

We need to embrace the unpredictability of basic cancer research and continue to invest in it. Otherwise, we will deny ourselves the opportunities to make those unexpected scientific discoveries that can, eventually, have a huge impact on people with cancer.

Without basic cancer research we have nothing to translate to the clinic. Finding the right balance and making everything connect is crucial for success.

This article is an edited form of a post which previously appeared on Professor Workman’s ‘The Drug Discoverer’ blog at icr.ac.uk .

Professor Paul Workman

Chief Executive

The Institute of Cancer Research, London

www.icr.ac.uk

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