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How our researchers gained top honour in UK science

06
May
2016

Last week it was announced that two of our leading scientists have been elected as Fellows of the Royal Society. Henry French discusses their research – and the crucial role it is playing in the search for new cancer treatments.

Posted on 06 May, 2016 by Henry French

Professors Jon Pines (left) and Paul Workman (photo: the ICR)

Professors Jon Pines (left) and Paul Workman (photo: the ICR)

Last week, The Institute of Cancer Research, London was abuzz with the news that Professor Paul Workman, our Chief Executive, and Professor Jonathon Pines, our Head of Cancer Biology, had been made Fellows of the Royal Society.

It’s a terrific honour for them both, and great news for the ICR.

Formed in 1660 by legendary natural philosophers including Robert Boyle, membership of the Society is a special honour reserved for scientists who have spent their career at the leading edge of their chosen field.

For Professor Workman, that field is the discovery of targeted cancer drugs — molecules that kill cancer cells by capitalising on specific weaknesses in their DNA, or in the communication systems they use to grow and spread.

After decades as a leader in this area, in 2014 he became the ICR’s Chief Executive, and on taking up the role laid out a scientific vision for drug discovery and treatment based on exploiting more potential cancer drug targets, designing new and innovative drug combinations, and developing ‘network’ drugs that hit cancer in more than one way at once.

Developing innovative drugs

Professor Workman began his career with posts at the Universities of Cambridge and Glasgow, and then held a senior leadership role at Zeneca Pharmaceuticals (formerly ICI, now AstraZeneca) before joining the ICR in 1997 to take charge of and build up what is now our Cancer Research UK Cancer Therapeutics Unit.

Under Professor Workman’s leadership, the Cancer Therapeutics Unit has become the most successful academic institution in the world at discovering new cancer drugs. Since 2005, we have discovered 20 cancer drug candidates, progressed eight drugs into clinical trials, and had abiraterone, a pioneering prostate cancer drug, approved by the US Food and Drug Administration and the European Medicines Agency – and also by NICE for use on the NHS.

Watch Professor Workman explain his research and what the new Fellowships mean for the ICR. 

A hallmark of Professor Workman’s approach has been to focus on discovering innovative drugs which work in completely new ways — in the expectation that major advances in benefits for patients will come from new types of drug, rather than from small iterations on what is already available.

In Paul’s initial work on cancer-causing protein kinases, he was instrumental in the discovery at AstraZeneca of the epidermal growth factor inhibitor gefitinib (Iressa), which is now approved for non-small cell lung cancer. He was subsequently closely involved in several protein kinase inhibitor projects at the ICR, including the discovery of inhibitors of AKT/PKB and Rho kinase that are now in clinical trials with Astex Pharmaceuticals and AstraZeneca, and of cyclin-dependent kinases that are undergoing clinical trials with Cyclacel.

Instigating clinical trials

Next, Paul focused on discovering some of the very first inhibitors of the lipid kinase PI3 kinase, which his ICR team developed for clinical use in many cancer types in collaboration with Piramed Pharma and Genentech. All of the above kinase inhibitors are showing considerable promise for clinical use.

Professor Workman is also well known for his research on inhibitors of Hsp90, which target many fundamental processes in cancer through their effect on the Hsp90 protein – a molecular ‘chaperone’ which interacts with many other proteins.

A multidisciplinary team of scientists led by Professor Workman successfully proved Hsp90 was targetable and that inhibitors were effective and well-tolerated — despite scepticism from the wider cancer research community — and their work has led to the development of several drugs which are now in clinical trials for a variety of cancers including lung and breast cancers. These include luminespib, which was discovered by Paul’s ICR team in collaboration with the company Vernalis.

Hsp90 inhibitors have the potential to act as network drugs that block evolution to drug resistance – a major goal of Paul’s current research.

A series of discoveries

Professor Pines's Royal Society Fellowship recognises his role in elucidating our knowledge of the machinery that controls cell division. Until recently, he led a team at the University of Cambridge dedicated to understanding this incredibly complex process.

While a PhD student in Sir Tim Hunt’s laboratory, Jon was the first to clone a protein called cyclin B — work which led to its identification as the crucial driver of cell division in all eukaryotes. He subsequently cloned the human cyclins while a postdoctoral researcher in California with Tony Hunter, and made the first links between them and cancer.

At Cambridge, his research increasingly focused on improving our understanding of how cell division is controlled in different parts of a cell over time. During this process DNA is duplicated, making two sets of chromosomes that are pulled apart on protein ‘rails’, and the cell membrane pinched and ultimately split into two cells.

Watch as Professor Pines describes his research and why he feels honoured to be elected to the Royal Society.

A network of highly controlled signals keeps everything in check, particularly to ensure that the ‘daughter’ cells receive an identical set of chromosomes from their ‘mother’ cell.

More recently, Professor Pines’s laboratory has had a particular interest in studying how the machinery that controls chromosome segregation works to destroy the right proteins at the right time, as a key element in the choreography of the process.

To do this, he pioneered a way to look at protein destruction in living cells by marking them with a fluorescent protein originally found in jellyfish.

The prospect of using his expertise in this fundamental area of cell biology to help in finding new cancer treatments is what brought him to the ICR last year, as our Head of Cancer Biology.

'Our researchers are excited'

Cell division is potentially targetable by cancer drugs because in gaining the ability to proliferate uncontrollably, cancer cells become dysfunctional, acquiring large numbers of genetic errors and consuming resources at a heightened rate.

Normally, the consequence of even minor genetic errors in cells is shutdown, with natural fail-safe mechanisms triggering programmed cell death — a process that is happening in our bodies all the time.

But cancer cells subvert these fail-safes in ways we do not fully understand, carrying on dividing while still acquiring more and more defects in their DNA. We believe that this genetic instability could be exploited by new therapies — by triggering natural cell death, and by scrambling cancer’s DNA and killing cancer cells as they go through the process of making copies of themselves.

This is the idea which brought Professor Pines to the ICR, and already has our researchers excited.

The next step

Both Professor Pines and Professor Workman have talked about the importance of the many different people who have contributed to making their research successful – including mentors, members of their labs and collaborative teams, and those who have provided logistical and family support.

The two professors represent different ends of the ICR’s scientific activity; in the one case, fundamental research into the biology of cancer; and in the other, translational research focused on discovering new cancer drugs.

What links them is the excellence of their research, and a shared desire to exploit our knowledge of cancer’s complexity to create a new generation of cancer treatments.

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