These findings set the groundwork to test retinoic acid therapy and its ability to coerce prostate cancer stem cells to modify into more specialized cells. This process, known as differentiation, can kill these cells or increase their vulnerability to chemotherapy.
ATRA (all-trans retinoic acid therapy) has been used successfully in patients with acute promyelomcytic leukaemia, improving survival rates from 0% to 80%. Prostate cancer is diagnosed in close to 40,000 men in the UK each year, with around 10,000 men dying annually.
Maitland recalls that low levels of vitamin A in the blood have always been associated with prostate cancer, but reasons why were unclear. This research has revealed the biological relationship between expressions of retinoic receptors and laboratory models of prostate cancers. Maitland and his team have discovered that the prostate transglutaminase, one of the most prostate-specific genes, is controlled by the retinoic acid signaling pathway.
"When retinoic acid gets into a prostate cancer cell, it binds to one of three receptors in the nucleus of the cell. This binding then triggers a sequence of molecular events inside the nucleus which results in the TGP gene being turned on or off. We have shown that the same situation also applies to a number of other genes. All of these genes then tell the cell how to behave - to divide for example."
In prior research, Professor Maitland has suggested that differentiation therapies have been misused in cancer treatments, but can be an effective treatment if used in small doses.
Previously, oncologists have used retinoic acid at a toxic level. In the future, they will need to learn to use low level doses strong enough to change the properties of easily influenced cells. Some cells may react unpredictably. Maitland and his colleagues will investigate these effects before this treatment can be used on patients.
Written by Kelly Fitzgerald