HYMS RESEARCH PROFILE

New hope to root out prostate cancer - Professor Norman Maitland

A RECENT BREAKTHROUGH by Professor Norman Maitland and Dr Anne Collins, based in the YCR Cancer Research Unit in the Biology Department at the University of York, opens up exciting potential for new therapies which would tackle prostate cancer at its root.

Through their work, funded by Yorkshire Cancer Research (YCR), not only have stem cells been extracted from human prostate cancers, but Professor Maitland's team have been able to lead the way - an international first - in propagating them in the laboratory, thus making a significant advance towards possible curative treatment.

The heterogeneous nature of prostate cancer has been accepted for years, and is present at various levels - anatomical, histopathological, genetic, and chromosomal. It has created uncertainty not only about the diagnosis of the disease, but also in determining prognosis and decisions about treatment.

Accepting the role of stem cells as pivotal may explain both prostate tumour heterogeneity and the variable responses of prostate cancer to different types of treatment. The team has worked on the hypothesis that tumour stem cells, which undoubtedly exist in many tumour types, including the prostate - and which constitute less than 0.1 per cent of a tumour mass - originate the spread of cancer. Thus if they can be identified and isolated, they can be tackled: and the team's achievement in recognising, highlighting and propagating the cells is a first major landmark in this process.

There are two models of genetic origins for cancers: the stochastic model, which assumes that every cell within a tumour can form new primary tumours; and the hierarchical or stem cell model, which assumes that only a rare sub-set of cells, the stem cells, can initiate more tumour cells. The tumour cell hypothesis isn't new - most tumour types are composed of diverse elements with different proliferative and malignant potentials, and this led to the hypothesis that only a rare, distinct subset of cells had the capacity to form tumours, the cancer stem cells.

Until now, in terms of treatment, prostate cancers have been considered to be homogeneous - created by a stochastic mechanism where it's impossible to predict the tumour-initiating cell. The conventional modes of therapy have tackled the mass of the tumour - for instance radiotherapy targets dividing cells, chemotherapy normally targets proliferative cells. Residual stem cells which do not divide at the same high rate can thus survive through treatment, and can start further proliferation.

Now, in the light of this discovery, Professor Maitland and Dr Collins will be able to investigate and evolve therapies that can be directed directly against the tumour stem cells. There may be genuine hope of long-term cure rather than the current palliative therapy, and the research may also have implications for the treatment of other cancers - tumour stem cells also occur not only in leukaemias, but also neuronal tumours and cancers of the breast and colon.

The Research Unit at the University of York was set up in 1980 by Yorkshire Cancer Research, an independent charity funding cancer research in Yorkshire. It provides around £4 million each year for research in the regions's five centres of research excellence, including both Hull and York. Professor Norman Maitland is a former chairman of the British Prostate Group and is co-ordinator of an international EU funded network to develop gene therapy for prostate cancer.

The findings of the research are published in Cancer Research, the journal of the American Association for Cancer Research, under the title Prospective Identification of Tumorigenic Prostate Cancer Stem Cells Cancer Research 2005 65: 10946-10951

Derived from mini-review: 2005 BJU International

March 2006

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