Professor Paul Workman - Informal Profile

Paul Workman is Deputy Chief Executive of The Institute of Cancer Research (ICR) and is also Head of the Division of Cancer Therapeutics, Director of the Cancer Research UK Cancer Therapeutics Unit, and Harrap Professor of Pharmacology and Therapeutics at the ICR. A leader in the field of molecularly targeted cancer drugs, he is a Fellow of the Academy of Medical Sciences, the Royal Society of Medicine, the Royal Society of Chemistry and the Society of Biology and is a Cancer Research UK Life Fellow. Paul's research focus is the discovery and development of cancer drugs that exploit our knowledge of the cancer genome and cancer biology and his passion is personalised medicine.

Paul was born in Workington, Cumbria and was educated at Workington County Grammar School. He then did a degree in Biological Sciences at Leicester University, specialising in biochemistry. Having been inspired by his laboratory research project in enzymology and excited about designing small molecule drugs to specifically kill cancer cells but not healthy cells, Paul then did a PhD in cancer pharmacology at the University of Leeds.

Further inspired by this to pursue a career working on cancer drugs, Paul then moved to Cambridge to establish  a new cancer pharmacology lab at the MRC Clinical Oncology Unit in the MRC Centre, located on the Addenbrookes Hospital campus and part of Cambridge University. He worked there for fifteen years, progressing from Postdoctoral Scientist and Staff Scientist to the MRC’s Special Appointment (Professorial) Grade. His main research focus during this period was on drugs that take advantage of the hypoxic (low oxygen) environment in cancer tissue — Paul helped to design and take into the clinic a number of hypoxia-targeted drugs.

After a brief US sabbatical in 1990 spent at Stanford University and Stanford Research International, located near San Francisco in California, Paul next moved to Glasgow University, where he took up a Cancer Research Campaign Chair in Experimental Cancer Therapy and became Director of Laboratory Research in the Department of Medical Oncology at the Beatson Laboratories. It was there that he began his long and successful research interaction with his clinical collaborator and friend Professor Stan Kaye. Paul says: “My experience in Cambridge, Glasgow and now here at the ICR and The Royal Marsden Hospital has taught me the tremendous value of a close and productive research interaction between the laboratory and the clinic. When this works well it highly productive, very motivating and incredibly rewarding. It is fantastic to see the results of our research giving real benefit to cancer patients.”

It was also in Glasgow that Paul started his research on drugs that block the cancer-causing aberrant molecular signalling in malignant cells, including work on designing early kinase inhibitors acting on the epidermal growth factor receptor (EGFR). Following this, Paul then had a four year period in industry as Head of the Bioscience Section in Cancer Research at the major pharmaceutical company AstraZeneca's Alderley Park site, located near Manchester. While there he was responsible for the biology of the project that produced the EGFR kinase inhibitor gefitinib (Iressa) that has received regulatory approval in non small cell lung cancer and was one of the first personalised cancer medicines, showing its strongest effects in patients with cancer-causing mutations in EGFR. While at AstraZeneca Paul also established and ran the Strategic Alliance with the then leading kinase biotechnology company Sugen. “I learned a fantastic amount about how to build, organise and run research in a big pharmaceutical company and also in a small biotech. That was invaluable to me” he says.

In 1997 Paul decided to utilise all the skills he had developed previously in industry and academia to build up a large non-profit drug discovery group at the ICR that would focus on exploiting the molecular abnormalities responsible for creating and maintaining cancer cells. He calls this “drugging the cancer genome.” His motivation was, he says, “the exciting potential to build on the outstanding basic research strengths at the ICR to discover innovative cancer drugs — combined with the opportunity to move our new drugs quickly into clinical trials in the Royal Marsden Hospital.” Paul also preferred to carry out his drug discovery and development research in an academic setting where the focus would be on research excellence and patient benefit, free from the short-term commercial priorities that inevitably affect the private sector.

The success of this enterprise is shown by the discovery of sixteen drug development candidates over the last six years, with six drugs entering Phase I clinical trial over a recent two year period. In addition, in 2011 the prostate cancer drug abiraterone, discovered earlier at the ICR, was shepherded through clinical trials to receive regulatory approval in the US, Canada and Europe. “This has been a very  exciting and productive period” Paul says.

The productivity of the ICR team was recently highlighted in an article on academic drug discovery in the prestigious journal Cancer Discovery. Noting not only the pipeline of new drugs emerging from the group but also the scale of the effort – the Unit is probably the biggest academic cancer drug discovery group in the world with around 160 staff – the article said, "ICR's breadth of attack is the exception rather than the rule among academic biomedical research institutions, it highlights a growing trend for these institutions to broaden their attack beyond basic discovery of drug targets, with funding from both public and private sources."

The research productivity of Paul’s team has also been recognised by the receipt of American Association for Cancer Research’s  6th Team Science Award 2012.  The citation for this prestigious Award said: “This team’s research is an outstanding example of how innovative cancer research conducted by a highly functioning translational team can start with biologic hypotheses and ultimately lead to much-needed cancer therapeutics.” The award citation went on to say: “Overall, the work carried out by this multidisciplinary team over the last six years provides an outstanding example of the non-profit cancer drug discovery and development model that they have pioneered, as well as exemplifying a meritorious ability to collaborate productively with industry to accelerate patient benefit.”

Many of the unit's drugs were discovered in collaboration with – or licensed to – biotech or pharma companies. The culture of team science and of entrepreneurial proactive interaction with industry is something that Paul has worked hard to promote. "Successful drug discovery requires the close collaboration of a large multidisciplinary team of scientists — biologists, medicinal chemists, clinicians and others – working closely together towards a common goal. Collaboration between academia and industry is also essential to accelerate patient benefit" Paul says.

Paul is currently working on drugs that block molecules that are essential for the growth and survival of cancer cells, in particular molecular chaperones such as Heat Shock Protein 90 or HSP90 which tumour cells are dependent on or "addicted to". In 2010, he received the prestigious George & Christine Sosnovsky Award in Cancer Therapy from the Royal Society of Chemistry, as the award citation says: “For his seminal research on the role of chaperone proteins in cellular processes and the application of this knowledge at the forefront of anti-cancer drug discovery". The leading HSP90 inhibitor NVP-AUY922 was discovered by Paul’s team in collaboration with the biotech company Vernalis and is now being developed in the clinic by Novartis. Other chaperone-related targets that Paul's group have shown cancer cells to be dependent upon are now being pursued by his Unit as drug targets. Watch Paul talk to eCancer tv at the 2010 San Antonio Breast Cancer Symposium, explaining what molecular chaperones are and their role in causing cancer and describing his research to discover inhibitors of HSP90 that are now showing promise in early clinical trials.

Another area that Paul is well known for is drugs that block the cancer-promoting PI3 kinase pathway that, again, many cancers are addicted to. The leading PI3 kinase inhibitor GDC-0941 was discovered by his team in collaboration with the start-up company Piramed Pharma and is now being developed clinically by Genentech.

“These are both examples of projects” Paul says “that were seen as very high risk at first and where we did early drug discovery research that not only led to our own drugs but also contributed to these targets being widely adopted by industry. This is an important role for drug discovery in the non-profit sector — to take early risks in a way that it is often difficult for industry to do.”

Paul has also been the scientific founder of two successful biotech companies: Piramed Pharma, which was acquired by Roche in 2008 and Chroma Therapeutics. He says: “I have used the diverse experience I’ve had to build up a great team at the ICR that combines the best elements of both academic and industrial drug discovery and development. I see this as essential to fill the innovation gap between basic research and the development of clinically effective drugs.”

“I find it extraordinarily satisfying to be involved in designing small molecule drugs that are able to correct or exploit a specific cancer-causing abnormality” he says. "I am excited about, and strongly motivated by, the therapeutic potential of these drugs for cancer patients as well as proud of the science behind them.” Paul is also motivated personally as both of his parents died of cancer.

Paul envisages that personalised medicine will rapidly become standard treatment for oncology patients. “It is now becoming clear that the choice of the most appropriate drug therapy will increasingly be based on the genetic causation and molecular make-up of the cancer — that is, on the genes and biochemical networks which are responsible for driving the individual tumour. That is a tremendously exciting prospect which is already becoming a reality” he says. “Effective therapy with our new molecularly targeted therapies requires the use of predictive biomarkers, alongside the drugs, so that each individual patient can be given the drugs that they are most likely to benefit from — which is the basis for personalised medicine.” This use of predictive biomarkers is part of an approach that Paul developed known as the “Pharmacological Audit Trail.” He describes this as: “A conceptual and practical framework for decision-making, based on biomarkers,  for rational drug discovery and for optimal clinical evaluation and use.”

Paul has no regrets about joining the ICR: “I love the passion and energy for cancer research, the high level of scientific expertise and the focus on achieving improved outcomes for patients. The close interaction with the Royal Marsden is very important for translating our research into clinical benefit. We have benefited hugely from a network of interactions with basic and clinical researchers in our combined institution. It’s a unique environment for cancer drug discovery and development and it’s a really exciting time to be doing this.”

In terms of how he divides his own time, Paul comments: “Through my varied experiences in research and having worked in different roles and diverse environments, I have learned about myself that it is really essential for me to run a personal research lab as well playing a broader senior leadership role. I am not happy unless I can run my own lab and my own research projects, finding out new things, and training the young researchers of the future. It’s also really important for me to be involved in multidisciplinary research, especially the interface between biology and chemistry which is critical for successful drug discovery.”

At the same time, Paul's interest and experience in research leadership led to him being appointed as Deputy Chief Executive of the ICR in March 2011. He says: “This was an offer that I could not refuse! To work with Alan Ashworth and the senior people at the ICR and The Royal Marsden to help accelerate personalised treatment and make a real difference to the lives of cancer patients — especially at this stage in the evolution of translational cancer research with our detailed knowledge of the cancer genome — was just too good an opportunity to miss.”

Paul believes the ICR has enormous potential to develop new drugs in the future that will contribute to patients receiving personalised treatment for their individual cancer.

When he is not working, Paul enjoys music, including opera, and he is a keen supporter of Manchester United. He tries to keep fit by going to the gym. Paul and his wife enjoy living in the countryside of the Surrey Hills, where his son, daughter and grandson are also based, while still being close to London with all its cultural attractions.