Tackling the root of the disease

Stem cells are a hot topic in cancer research, and with the launch of a specialised consortium of world-leading scientists to push the frontiers of this research, it looks set to become even hotter.

Cancer Research UK and its commercial arm Cancer Research Technology (CRT), have set up a team of stem cell experts across the UK. By putting their heads together to share their knowledge and expertise in this field, the team will undertake cutting edge research to identify new targets to detect, monitor and treat cancer. The project will initially run for two years – with the intention to be extended for longer.

The charity has hand-picked four world-class research groups to unravel the role of cancer stem cells in the development, growth and spread of tumours in breast, prostate and head and neck cancers.

Professor Fiona Watt, deputy director of Cancer Research UK’s Cambridge Research Institute will lead the team. The other members in the consortium are: Dr Robert Clarke, senior lecturer and breast biology group leader at the Paterson Institute for Cancer Research and University of Manchester; Professor Norman Maitland, director of the Yorkshire Cancer Research Unit and Professor of molecular biology at the University of York; and Professor Alan Clarke – Professor of genetics at Cardiff University.

The project promises to be fascinating – one reason being that emerging research suggests scientists may need to broaden the pool of cell proteins they currently fish in for targets to be used for the development of new cancer drugs.

Most current cancer therapies target dividing or proliferating cells, which suggests scientists may, to date, have overlooked a totally different type of cell when searching for new targets for the development of new cancer drugs.
While it was previously thought that all the cells within a tumour are the same, it is now known that tumours are heterogeneous – they are made up of many different types of cells.

Within tumours a small number of slow-growing cells do not respond to standard treatments. It’s now thought there’s a number of malignant cells with stem cell properties in most tumours. And the recurrence of tumours that have apparently been completely removed or destroyed by surgery, radiotherapy and chemotherapy could be explained by a very few of these residual ‘cancer stem cells’.

Put simply, cancer researchers subscribe to the ‘dandelion theory’ – which states that current cancer therapies kill the cancer cells – or the ‘flower’ which renders the disease manageable – yet there remains the possibility that new tumours can regenerate from the ‘roots’ – or ‘cancer stem cells’. But by targeting the weaknesses to destroy the cancer stem cell itself, the theory is that one day scientists will develop treatments which reduce the likelihood the disease will return.

At the moment not that much is known about the way cancer cells can be identified and killed. For example it’s not understood if these cancer stem cells are the result of faults developing in the healthy stem cells that are present in adults in all regenerating tissues and renew that tissue – for example skin and blood cells. Or whether they are the result of faults in mature cells which have become cancerous and developed stem cell-like characteristics.
 
While the existence of cancer stem cells is well understood in blood cancers – which can be identified by cell surface markers – there is less understanding among the academic research community in solid tumours.

Some early laboratory studies show that select and very limited populations of tumour cells can re-establish tumours. But other studies challenge this observation and show that instead that a high percentage of tumour cells have this ability to self-renew.

The disparity might be explained by differences between different types of tumour – for example skin cancer could have different characteristics compared with other tumour types. But to find out if this is the case there is a need to isolate, study and characterise tumour stem cells from freshly removed tumour biopsies.

And the Cancer Research UK/CRT Cancer Stem Cell Consortium will do just this. The team will develop tests and models to refine a common set of known proteins – or biomarkers – present on cancer stem cells across three different tumour types for future drug discovery programmes.

The signals of particular interest to scientists are Wnt and Notch – they are involved in self-renewal and faulty in stem cells. As such they provide an opportunity for new targets in drug discovery projects. And the team will also identify new biomarkers as potential targets for the development of new cancer drugs.

Professor Watt said: “Conventional treatments – which do not target cancer stem cells – may shrink a tumour initially but they don’t prevent regrowth or spread of the tumour.”

“At the moment there is limited information on the ways scientists could target cancer stem cells. But I hope that knowledge generated by our team of experts will help in the development of potential new therapies to treat difficult to beat cancers.”

The project will initially receive £500,000 from Cancer Research UK. It is hoped each research team will attract an industry partner to bring in additional skills, know-how and more funding for longer term research.

In return these industry partners will benefit through access to the consortium’s latest discoveries and intellectual property – as well as sharing Cancer Research UK’s expertise in translating scientific discoveries into new cancer treatments. Once the early development phase is complete, the industrial partner can choose to develop any joint discoveries into compounds with the potential to be taken into early clinical trials.

Dr Phil L’Huillier, Cancer Research Technology’s business development director, said: “We’ve selected the world’s leading experts in cancer stem cell research to push the frontiers of knowledge in this important field.”

“Targeting cancer stem cells is an important strategy in the fight against cancer. By bringing together industry partners and using our commercial expertise alongside the critical mass of the best brains in science we hope to identify important new leads for the development of new therapies to increase survival from a range of cancers.”

Any profits from the success of the projects will be shared between the charity and the research partners involved, with Cancer Research UK re-investing any proceeds in its future research work. The business relationships will be managed by CRT, which has more than 20 years experience in licensing patents and developing opportunities for new cancer drugs and diagnostics, working closely with licensees and the pharmaceutical industry.

This is the second of CRT’s consortia, the first called Senectus Therapeutics Ltd formed in 2008 to further research into the triggers of cellular senescence – cell aging – a process by which cells irreversibly halt their cell cycle of growth and division.

Harpal Kumar, Cancer Research UK’s chief executive, said: “Cancer stem cells represent an exciting new frontier in our efforts to beat cancer.  We urgently need to find new and effective ways to target these cells. This early research will pave the way for our scientists to develop more treatments and help more people survive a diagnosis of cancer – especially people who have aggressive cancers or for whom conventional treatments do not prevent the cancer returning.

“We’re investing in this exciting collaboration made up of world-leading scientists to combine our research expertise with support from industry partners to crack the codes behind the causes and development of cancer.”