New study to turn cancer research on its head

David Binning (Australian Life Scientist)
02 August, 2010 16:30

Research challenges conventional wisdom that cell death impedes tumour growth

Researchers at the Walter and Eliza Hall Institute (WEHI) have shown that programmed cell death or apoptosis, a process which has typically been assumed to prevent or slow the development of cancer, may in some instances contribute to its spreading.

“In general everything we’ve known indicates that if you have impaired cell death that helps the tumour to get going,” Professor Jerry Adams told Australian Life Scientist. “What’s exciting about this result is it’s the first case in which the opposite happens.”

For example, when the DNA in many cells is damaged, as occurs after repeated exposure to low doses of radiation, this leads to repeated cycles of cell death in the body’s tissues.

“Attempts by the body’s stem cells to repopulate the depleted tissue can then actually drive the tumour development,” project leader Professor Andreas Strasser said.

“That’s because the radiation, while killing many cells within a tissue, will create mutations in some of the surviving stem cells. When such abnormal (mutated) stem cells repopulate the tissue, they will divide many times and this can promote the development of tumours.”

A particular focus of the teams’ research was comparing the effects of radiation exposure in mice with and without the so-called Puma gene, which is essential for the death of cells with damaged DNA.

“If normal mice (which have the Puma gene) are given a low dose of radiation it destroys around 80 per cent of the white blood cells,” Professor Strasser said. “That does not kill the mouse but it does mean the stem cells in the bone marrow have to work extra hard to replenish the blood system. This can lead to the formation of tumours of white blood cells, called leukaemia’s, if the stem cells doing the re-populating have cancer-causing mutations."

In contrast, mice without the Puma gene did no experience this type of tumour development at all.

“If mice don’t have the Puma gene when they receive low doses of radiation the white blood cells are not destroyed, so you don’t force mutated stem cells to become activated (and divide) to replenish the blood system,” Professor Strasser explained.

The findings point to an increased risk of cancer development in people who have experienced cycles of cell damage followed by tissue re-population by stem cells. Examples include liver cancers such as those arising from viral infections like hepatitis C, or alcohol-related liver damage. The research may also help to shed light on the causes of secondary cancers which can appear in patients cured of their primary cancer by chemotherapy drugs which typically result in damaged DNA.

Further, these findings are expected to lead to a deeper understanding of the role and effectiveness of the new class of BH3 mimetics cancer drugs, which are designed to kill cancer cells.

Professor Adams said that the study results would likely be of interest to Abbot Laboratories, which is currently conducting similar research into cancer treatments. Abbott and the WEHI have a research collaboration agreement.

Funding for the WEHI study was provided by the National Health and Medical Research Council, the Leukaemia and Lymphoma Society, the National Institutes of Health (US), the Juvenile Diabetes Research Foundation, Cancer Council Victoria and the Victorian Government.

The complete findings were published this week in the international journal Genes and Development.

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