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The Role of Stem Cells in Cancer
By Sabina Michnowicz
This week on the Naked Scientists we're looking at stem cells and cancer, we'll have some of the top experts telling us about their research, including studio guests Andrew Futreal and Fiona Watt. Andrew has just published the results of his survey of the human genome in cancer and Fiona will be telling us about her work with stem cells and skin.
Stem Cells have featured heavily in recent media; they have the potential to cure many illnesses for which treatment is currently limited. This potential lies in their unique ability to become any type of specialised cell (such as a skin cell, a blood cell or the cell of an organ such as the lungs or kidneys) Like all ideas with massive potential to change the fundamental way things are done (in this case the types of medical treatments available) it is packaged with the pre-requisite moral controversy which prevents that potential being fulfilled before all the possible detrimental outcomes have been addressed. Which is, of course, the way it should be. But don't let the recent media interest let you think that stem cell treatment is a new idea – it isn't; bone marrow transplants which have been taking place since 1968 use stems cells. Taken from either the patient or a donor, the bone marrow stem cells can turn into any sort of blood cell and replace those damaged by cancers such as leukaemia. New stem cell therapies include skin grafts for burns and treatments for Parkinson's disease.
Cancers result from genetic mutations – so here's looking at those mutations, gene by gene:
There are however, many studies going on for new types of therapy and that's where we come in, as this week's Naked Scientists Radio Show and Podcast will be exploring the cutting edge advances in stem cells and how they can be used to treat cancer. We'll have Andrew Futreal (from the Wellcome Trust's Sanger Institute) telling us about how he worked on the broadest survey yet of the human genome in cancer, which involved sequencing over 250 million letters of DNA code, covering over 500 genes and 200 cancers (that's a lot of sequencing!). His findings reveal that there are far more mutated genes which drive the development of cancer than previously thought. Also, interestingly, he found that there are many other mutations in the cell as well – these are termed 'passenger' mutations as they don't drive (or cause) the cancer – they just come along for the ride. Figure one shows the sequence of one such mutation 'ERBB2' studied.
Cancers are believed to occur as a result of genetic mutation and having sequenced all of the human genome scientists can analyse thousands of genes. This should lead to a 'catalogue' of the mutations in individual cancers. The team identified possible driver mutations in 120 genes, most of these had not been seen before. Most mutations turned out to be passengers, but the fact that there were far more drivers than previously thought suggests that many more genes contribute to cancer than previous knowledge showed. This provides a vital insight into how cancers develop, the next challenge will be to distinguish the drivers from the passengers. The development of new, faster DNA sequencing technologies, will allow a large-scale comprehensive study of cancers at DNA level – this findings of such a study are likely to lead to massive changes in the diagnosis and treatment of caner.
Stem cells are the ones in the careers library, deciding what to be when they grow up:
There are different types of stem cells including epithelial (skin) cells and these can become specialised; for example they may become interfollicular epidermis, sebaceous glands or the lineages of a hair follicle. It is epithelial stem cells that Fiona looks at, focusing on the factors which regulate the behaviour of cells in the epidermis. By comparing how normal epithelial cells function with the processes going on in cancer cells her work will help to provide important information about skin cancers, including how the cells differentiate, proliferate and how they are assemlbed to form tissue. She does this in a variety of ways including clonal analysis and gene expression as well as analysis of human tumour material. So far she has identified markers of the stem cell compartment and shown that stem cells have a highly patterned distribution. The next stage is to look at how stem cells make the decision to differentiate or stay in the stem cell compartment, what determines lineage selection, how spatial organisation is established and maintained and finally how stem cells and their neighbours contribute to the development of cancer.
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