Analysis: researchers are investigating targetted drugs to prevent the build up of calcium in cells which promotes prostate cancer
There are tiny gates on the surface of every cell that permit atoms, or molecules to pass in and out. If these gates are wide open then charged calcium ions can flood in, stimulating prostate cancer to grow. Our research aims to - literally - keep the gates closed to cancer.
Calcium is perhaps best known as a component of milk that supports bone health. Inside the cell, it is also essential for cell growth and proliferation. We have found that prostate cancer grows when calcium is disrupted.
We tend to think of prostate cancer as one of the more benign cancers as it's survivable in most cases, but it remains a killer. The death rate of about one in 41 means about 100 of the 4,000 men in Ireland diagnosed annually die from this cancer.
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From RTÉ Radio 1's Today With Claire Byrne, dealing with a prostate cancer diagnosis
One important treatment for prostate cancer is called androgen-deprivation therapy (ADT), androgen being a natural hormone in the body whose action stimulates prostate cancer to grow. This is the first line of treatment used in men whose prostate cancer is advanced, due to late diagnosis, or is aggressive. While this treatment is often effective initially, the cancer learns to grow in some men without the need for androgens and develops resistance to the treatment. At this stage, the disease is referred to as castrate resistant prostate cancer and the diagnosis is terminal. There is an obvious unmet need for new treatments for these patients, and that is our focus.
The gateways, or tiny biological toll bridges, on the surface of the cell which allow charged atoms, known as ions, like calcium and potassium, to pass in and out are essential for the cell’s survival. When something disrupts these channels, it gives prostate cancer an opening. We found a particular calcium channel in prostate cancer patients who have developed resistance to ADT. This channel, which comes with a suitably opaque scientific name (CaV 1.3), is not functioning as it should so we wanted to find out why this is happening and how to fix it.
We know that cancer exploits changes in the normal balance of calcium going in and out of these gateways. We also know that too much calcium in the cell will promote cancer, but too little will kill cells. Interestingly in prostate cancer, these calcium channels are stuck open, allowing excessive calcium into the cell, promoting progression to a castrate resistant form of prostate cancer, with limited treatment options. Thus, if we can develop targeted drugs to close these gates, we know that we can slow tumour growth.
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From RTÉ Radio 1's Today With Sean O'Rourke, Dr Máire Finn GP answers listeners' queries about prostate cancer
It is helpful for our research that there are already drugs on the market that act on the calcium channels we are interested in. We believe these drugs could be adapted for use against resistant forms of prostate cancer. This is termed drug repurposing, which can result in the advent of a new treatment in half the time it would take to develop a drug from scratch. Our aim in the next five years is to identify an existing drug that can be used in this manner to target calcium channels involved in driving prostate cancer.
This development of new drugs targeting a specific change within a cancer forms the basis of a treatment approach called personalised medicine. A big challenge when treating cancer arises from the fact that each patient carries different mutations in their genes so the biology driving the growth of cancer differs from person to person. Current treatments, such as chemotherapy for example, provide a 'blanket bombing’ method that kills cancer, but also healthy cells, without targeting the specific cancer biology. This can mean that some patients do not respond completely to their treatment, leading to treatment resistance and patient mortality.
Identifying specific changes that promote prostate cancer can enable the development of new therapeutics to prevent their action
Identifying specific changes that promote prostate cancer, such as altered calcium channels, can enable the development of new therapeutics to prevent their action and stop cancer. This can ensure patients respond to their treatment, which prolongs their survival and helps to reduce often debilitating and unnecessary side effects.
As part of this personalised medicine approach, these changes are detected by measuring differences in patient tissue, blood and urine samples, known as "biomarkers". This will enable medical professionals to quickly identify specific changes in a patient’s cancer biology which leaves them vulnerable to developing castrate resistant prostate cancer. This helps to guide the personalisation of a patient’s treatment and prevent the development of resistant prostate cancer. Thanks to the research on calcium channels in cancer, it is becoming evident that these gateways can open a pathway to the development of new biomarkers and treatments for patients who are currently - sadly - out of options.
The full paper on which this piece is based can be read here.
The views expressed here are those of the author and do not represent or reflect the views of RTÉ
