Calcium fights prostate cancer

Aug 15 2005

Calcium, more familiar in its role as one of the building blocks of the body, is being enlisted as a tool in the fight against prostate cancer.

Researchers in Flinders University's Department of Medical Biochemistry are investigating a pharmacological approach that will use calcium ions within cancerous cells in the prostate to kill those cells.

"There are a series of what we call calcium channels in the surface of the prostate cancer cells, which effectively regulate the level of calcium within the cells," Professor Greg Barritt said.

His research team is working to develop a procedure that will overactivate the channels, thereby producing levels of calcium that are toxic to the cancer cells.

Professor Barritt said that in an ageing population that increasingly survives other diseases, prostate cancer is emerging as a major cause of death for men.

Along with surgical removal of the prostate, he said hormone ablation, the treatment that removes the androgen hormones - chiefly testosterone - on which the cancer is dependent, acts as a good first-line defence.

"In most patients, the cancer will regress after this treatment, particularly if the cancer is caught early," he said.

In some patients, however, disease reoccurs as remnant cancer cells mutate to become hormone independent.

"At the moment there are limits to what we can do in terms of treatment for some people with hormone refractory prostate cancer," Professor Barritt said.

"Our research is directed towards a treatment for that form of prostate cancer, and it may well be used in conjunction with other treatments such as chemotherapy."

According to Professor Barritt, the new strategy effectively mimics calcium's role in cell degradation which occurs naturally, for example, in the degradation of nerve cells in the body.

Professor Barritt said the public tends to think of calcium in a beneficial role, particularly in regard to the structure of bones and the crucial role of Vitamin D in the diet.

And indeed calcium, in its intracellular form, is vital throughout the body - it is present in most cells of the body including the nerves and skin, and the contraction of heart and skeletal muscles is dependent on intracellular calcium.

Yet calcium can also play a more destructive role: "One of the functions of calcium - a normal one in most instances - is to help cells to die," Professor Barritt said.

When new nerve pathways are developed, for instance, the old ones become redundant, and calcium acts as the terminating agent.

"We are basically activating the same pathway when we are trying to kill the cancer cells," Professor Barritt said.

He said that there are still challenges to overcome before the approach can take its place among the battery of treatments used to combat cancer of the prostate.

One of the problems is accurate targeting of the prostate. While incidentally killing the normal cells of the prostate gland along with the cancerous cells does not appear to be a problem - surgical treatment of cancer involves wholesale removal of the prostate in any case - it is still necessary to confine the effects of the treatment.

"One of the methods we are using to achieve that specificity is, in part, a gene targeting method. In principle, we are using what we call promoters of protein expression specific to the prostate cells, which switch on protein synthesis in prostate cells but not in other cells."

There is also a second, chemical method that uses the cancer itself, relying on proteins produced only by prostate cancer cells to achieve accurate targeting.

Professor Barritt said that prostate cancer begins with a phase known as benign hyperplasia, when genetic or environmental factors trigger the prostate cells into growing larger and multiplying.

If unchecked, the cells may become carcinogenic and invasive, affecting tissue around the prostate and travelling in the blood to other sites in the body, favouring the bones and particularly the nearby spine.

"This is the invasive, metastatic stage, and we really need to be developing a treatment that targets those cells as well as the ones in the prostate, which makes the challenge of targeting even more complicated," Professor Barritt said.

The calcium channels have emerged in yet another possible role, this time as an aid to diagnosis and prognosis in prostate cancer.

Professor Barritt said that as prostate enlargement progresses to its more aggressive stage, the cancerous cells display a higher expression of the calcium channel.

"If you are able to measure the amount of the channel that is present, it might be a useful predictor of the cells' future behaviour," he said.

"In patients who have had the prostate removed and have undergone hormone ablation therapy, you may be able to predict whether that person is going to go into a strongly metastasising and invading tumour, and then apply some appropriate treatments at an early stage, rather than waiting for it to happen."