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European Biopharmaceutical Review

Stem Cell Elimination

 

DEFINITION

There are at least two theories that try to explain tumour formation and growth. The first is the stochastic model, which assumes that all cancer cells have a low but equal tumour forming capacity; the second is the cancer stem cell or tumour initiating model. This theory suggests that there is a small population of cells within a tumour responsible for its generation and maintenance, and that these cells are also capable of forming new tumours. All other cells in the tumour lack this capacity. Hence there is a cellular hierarchy within a tumour, with all cells ultimately derived from this small population of cancer stem cells. In recent years, more and more publications have provided evidence in support of the cancer stem cell/tumour initiating cell hypothesis, and this report will summarise some of the literature and techniques used in the analysis of cancer stem cells. From here on, this model will be referred to as the cancer stem cell model, but this is interchangeable with the tumour initiating cell model.

The term ‘cancer stem cell’ and its definition – “a cancer stem cell is a cell within a tumour that possesses the capacity to selfrenew and to cause the heterogeneous lineages of cancer cells that comprise the tumour” – were determined by a group of non-stem cell and stem cell scientists at a scientific meeting in 2006 (1). This term describes the function of these cells well, but unintentionally causes some confusion, as it suggests that a cancer stem cell is derived from a stem cell (2). Rather, a cancer stem cell is any cell which has acquired the characteristics of a stem cell within a tumour and meets the criteria in the definition above. WHY STUDY CANCER STEM CELLS? It is acknowledged that while existing cancer therapies reduce the bulk of the rapidly proliferating and differentiating cells within a tumour, they may not have an effect on the cancer stem cells, which are possibly more dormant or resistant to treatment. The ability to reduce tumour mass, while allowing these cells to survive, may explain why many tumours recur following treatment (see Figure 1). Identifying agents that can remove the cancer stem cells from a tumour may provide an effective strategy in the treatment of cancer, and such agents may be curative rather than palliative.


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Kirsty Holden is a Senior Scientist in the Contract Research division of Epistem Ltd, and has worked there for two years. She has a BSc (Hons) in Biochemistry from UMIST, Manchester and a PhD in Mammary Cell Biology and Apoptosis from the University of Manchester. She worked at SmithKline Beecham between her BSc and PhD degrees and held a post-doctoral research position in mammary gland biology, extracellular protease activity and wound healing at the Finsen Laboratory, Copenhagen, prior to joining Epistem.

Kevin Jones is a Senior Scientist in the Contract Research division of Epistem Ltd. He has a BSc (Hons) in Pharmacology from the University of Liverpool and a PhD in Intracellular Accumulation of the HIV Protease Inhibitors and the Effect of Active Transport, also from the University of Liverpool. Kevin worked in the DMPK department at AstraZeneca Pharmaceuticals for seven years following his PhD. His role involved developing new assays and focusing on the effects of active transporters on the absorption and distribution of NCEs.

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Kirsty A Holden
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Kevin Jones
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