Funded Research 2006

Isolation, culture and molecular characterisation of castration refractory prostate cancer (CRPC) stem cells from clinical tumour material.
Dr Johann de Bono, Dr Sian Rizzo and Dr David Hudson, Institute of Cancer Research, Sutton

Stem cells are a small population fo cells that divide very occasionally throughout the life of a tissure or tumour. When they divide they replicate themselves but also produce transit-amplifying (TA) cells that are capable of limited growth. Ultimately, however, the TA cells will undergo a maturing process to become non-dividing PSA secreting cells that will finally die.

The aims of the Hudson team are to characterise prostate epithelial stem cells and to identify potential therapeutic targets that will allow us to either kill the stem cells directly of to induce them to undergo maturation to differentiate.

It is becoming clear that stem cells are present not only in normal tissues but also in cancers where they are responsible for driving cell division. The implication of the existence of cancer stem cells (CSC) is that current treatments may not be targeting the right cells. The slow cycling rate and expression of drug resistance genes means that stem cells may be able to evade some drug based therapies. They are also believed to be androgen independent and therefore will not respond to androgen ablation therapy. Although current treatments lead to the loss of the transit amplifying population resulting in a dramatic reduction in tumour size, CSC could survive and contribute to a relapse of the disease after treament ceases. Alternatively the stem cells may accumulate further genetic changes that confer resistence of the TA cells to treatment allowing them to evate therapy.

We believe that treatments could be dramatically improved if we can target stem cells. It is therefore vital that we find ways of targeting these treatments directly to the stem cell population.

We have collected needle biopsies from over 50 patients who have relapsed after their initial treatment, and we are using this tissue to grow cells and determine changes in their DNA leading to treatment failure. We have successfully cultured cells from over 20 of these samples and isolated stem cells. We are now in the process of identifying differences in the gene expression patterns of stem cells from normal prostate and cancers to identify specific markers that we can use as potential therapeutic targets. While growing these cells it is also possible to generate cell lines that will continue to grow indefinitely. Such cell lines will be extremely useful for drug testing and for examining the genetic changes leading to cancer as there are very few immortalised cell lines originating from hormone resistant prostate cancer.

We have also isolated DNA from these patients, including some for whom we additionally have smaples before their disease was treated. We have found some interesting changes and are now analysing all of the samples to identify changes that are more common than others and which may be required for the progression of the disease. We then plan to screen large numbers of patients to determine if the changes can determine the outcome of their disease.

Institute of Cancer Research, Prostate Stem Cell Team website >

 

Project commenced
August 2006

Length of project
2 years

Amount Supported
£99,000

 

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