Professor Ian Mackenzie points to a little jumble of cells on a computer screen and smiles. ‘They’re cancer stem cells,’ he says. ‘Not everyone in medicine believes in them yet, but look — there they are.’ Even to the untrained eye, it’s clear there are two distinct types of cell; one that groups together a little like frogspawn, and another that looks like a slug. ‘If you watched the slug-like one for long enough, you’d see it move,’ says the professor. ‘We believe this type of stem cell facilitates the spread of cancer and that the other is responsible for the growth of tumours and for making them return after you think your cancer has gone away.’
Stem cells, which are found in tissue all over the body, can grow into every kind of cell, including bone, skin and blood cells
In Professor Mackenzie’s laboratory at Barts and the London Medical School’s Blizard Institute, researchers are busy extracting these cells from tumours. Their work represents a potentially extraordinary new approach to the disease. The traditional view among oncologists is that cancerous tumours are the result of genetic mutations within ordinary cells that cause them to divide uncontrollably and then spread. However, evidence has been mounting that small numbers of stem cells within tumours actually orchestrate their growth and proliferation. But these types of cell are difficult to eradicate with traditional chemo and radiotherapy — they actually come equipped with pump-like mechanisms on their surface that filter medicines away — and they can re-grow even after the primary tumour has been destroyed or removed.
The discovery of stem cells' potential has led to hopes for new therapies
So, runs the latest thinking, if you could kill them, you could kill cancer. Stem cells, which are found in tissue all over the body, can grow into every kind of cell, including bone, skin and blood cells. The discovery of stem cells’ potential has led to hopes for new therapies that could rejuvenate and repair defective parts of our bodies and treat a range of illnesses from diabetes to Parkinson’s disease. But there is a certain irony. For while researchers around the world are devoted to finding new ways to grow stem cells, Professor Mackenzie’s team is determined to find ways of obliterating them. The theory is not yet universally accepted, but work by Professor Mackenzie and his colleague Dr Adrian Biddle — and supporting research from teams in York, Manchester and Cambridge, Texas and Massachusetts in the U.S., and Graz and Utrecht in Europe — is gradually convincing the medical fraternity that stem cells could hold the key to a cure for cancer.
‘When stem cells do something to repair damage to part of your body or to tackle Alzheimer’s or Parkinson’s, potentially there could be nothing better,’ explains Professor Mackenzie, a stem cell biologist. ‘But when their function is to grow and spread cancer, there could be nothing worse.’ Dr Biddle — who trained under Sir John Gurdon, last month awarded the Nobel Prize for his work on stem cells — recently published research that demonstrated the existence of the slug-like cells (‘epithelial mesenchymal transition cells’). ‘All stem cells seem particularly resistant to current drug therapies but these (slug-like) types are very nasty indeed,’ says Professor Mackenzie.
‘We’ve found both types of cell in head and neck tumours, and others have found them in breast, colon and several other types of cancer. 'If we could find ways to target them, we might have an elegant solution to the problem of cancer and its growth. The question is, how can you target cancer stem cells without damaging normal stem cells? We don’t know yet. But cancer stem cells do have a different metabolism, so the hope is we can target and exploit these differences.’
Researchers into blood cancers such as leukaemia have been aware of the role of stem cells in the disease’s progression for several decades. But evidence for stem cells’ role in the growth and spread of solid cancers such as colon, head and neck, brain, testicular and breast has been around for only a few years, and much of it is not accepted by some oncologists. ‘Cancer stem cells are a very controversial topic because the cancer stem cell model of tumour growth may not be applicable to all kinds of cancer,’ says Dr John Stingl, of Cancer Research UK’s Cambridge Research Institute. ‘There is very good evidence for cancer stem cells in blood cancers like leukaemia, and in brain and colon cancer, but the data supporting cancer stem cells is more controversial when you look across the whole range of cancers. One main difficulty in studying cancer stem cells is identifying them. For example, you might take a tumour and break it down into single live cells. Then you might put 100 of these cells into a dish with nutrients and find that only five grow, and conclude that those five with the capacity to grow must be the stem cells you’re looking for. But it is just as plausible that you used the wrong nutrients — perhaps they all would have grown had you used different nutrients.’
He adds: ‘This type of cancer stem cell growth may be prevalent only in some types of tumours and tumours at certain stages of development. For example, at the early stage of a tumour’s development it might be that a small number of these cells are triggering growth. However, by the time the tumour has become very aggressive, most of its cells might be stem cells. All of this confusion means there is a need for much more research. I personally think that at some point some very effective cancer stem cell-based therapies will be developed that will be applicable for some, but not all types of tumours.’
Back in Professor Mackenzie’s lab, he and his colleagues are satisfied that the images they are showing me are, indeed, cancer stem cells, not least because repeated experiments have found that when implanted into mice, these cells cause cancers to grow. ‘In pretty much all cancers where researchers have looked for stem cells, they have found them,’ says the professor. ‘So now we know these are the cells that need to be killed, we can try to find ways to kill them or stop them multiplying. We could take a long time testing thousands of compounds, but it is more likely that we will start with existing cancer therapies to find out and develop what is most effective in fighting them in a dish. Then we can begin thinking about clinical trials in patients. I would guess we’re looking at seven to eight years before we see trials of drugs for breast, colon, prostate, head and neck, skin and lung cancer. But if we’re lucky, it could be quicker.’
In the meantime, funding across all areas of research is tight and the budget for Professor Mackenzie’s modest research lab is just £250,000, provided by Barts and The London Charity, the Saving Faces charity and the Fanconi Anemia Research Foundation — but not the NHS. Compare his budget with the investment GlaxoSmithKlein put into the American cancer research company OncoMed in 2007 — $1.4 billion to develop cancer stem cell therapies. So far, GSK believes it was money well spent. ‘The research is focused on developing antibodies that could be used as medicines that attack cancer stem cells,’ a spokesman said. ‘It’s an exciting area of drug discovery. Researchers are looking at its potential in patients with advanced pancreatic cancer, but it’s an approach that has the potential to be developed against a range of tumour types.’
Source: Daily Mail UK