Dr Macaulay will carry out a clinical trial to test a new drug that blocks Insulin-like Growth Factors (IGFs) in men who are diagnosed with prostate cancer and are scheduled for surgery. There is usually a 4-week interval between deciding to have surgery and having the operation, so the researchers will use this window to administer the anti-IGF treatment.

The team will perform tests on the blood and prostate samples of men recruited to the trial. They will compare initial samples taken when the men first had a biopsy, and samples of blood and tissue from the prostate cancer removed at surgery after 4 weeks treatment, to measure changes in genes and proteins associated with aggressive cancer growth.

Dr Macaulay’s team aims to find out whether blocking these cancer-promoting growth factors could prevent harmless prostate cancers from becoming harmful. IGFs are proteins that are made by the liver in response to growth hormone, and are required for normal growth and development. These processes are kept under tight control in healthy tissues, but cancer cells can escape normal growth controls. One of the ways cancers do this is by reacting to high levels of IGFs, either by making IGFs themselves, or by responding to IGFs released into the bloodstream by the liver. It is known that people with very low blood IGF levels are strongly protected from developing cancer, while men with high blood IGFs are at increased risk of getting prostate cancer. High IGFs may also be involved in the recent finding that tall men are more likely to develop aggressive, fatal prostate cancer.

It is not yet known how high IGFs have these effects. Earlier studies from Dr Macaulay and others lead her to suspect that IGFs may not make healthy cells turn cancerous in the first place, but may encourage cancers to grow and spread, probably by activating a protein called IGF receptor (IGFR). Dr Macaulay’s team showed that prostate cancers contain more IGFRs than normal prostate tissue. They suspect that in men with high IGFs in the prostate or bloodstream, IGFRs are switched on, triggering critical events that make cancers more aggressive. By testing the IGF blocker drug, they aim to identify these critical changes, some of which may be targets for developing new treatments.

The researchers want to make sure that they carry out tests that will give them the most useful information. One practical problem is that prostate biopsies are very small, limiting the number of tests that can be done. To get around this problem, the team will also test the IGF blocker drug on prostate cancers grown in mice. These are less variable than human cancers, so seeing a big change in any genes or proteins in the mouse samples will help to prioritise tests to carry out on the patients’ samples.

By the end of this project the researchers will know whether the IGF blocker drug switches off IGFR in the prostate cancers, which genes and proteins are affected, and whether blocking IGFs reduces cancer growth in other ways, for example by reducing the blood supply to cancers, or affecting the immune system or metabolism. Dr Macaulay’s team will then apply for further funding to investigate these effects in more detail. In the longer term, blocking IGFs could help men who are on active surveillance for small prostate cancers, to reduce the risk of the cancers becoming aggressive and threatening life.

Reference - RIA16-ST2-024
Researcher - 
Dr Valentine Macaulay
Institution – University of Oxford
Award - £468,673