There are currently two main forms of radiotherapy for prostate cancer: external beam radiotherapy and brachytherapy. During external beam therapy, high-energy X-ray beams are aimed at the prostate from outside the body whereas in brachytherapy, radioactive beads are positioned inside the prostate. Radiotherapy works by damaging the DNA of the cancer cells. The cancer cells cannot repair themselves, so they are destroyed.

Unfortunately, healthy cells in the same area may also be damaged by radiotherapy, which can then lead to both short-term and long-term side-effects. Short-term side effects can include sore skin and feeling tired. Long-term side effects can include bladder and sexual changes. Also, not all cancer cells are killed, and so the cancer can grow back more aggressively.

Prostate-specific membrane antigen (PSMA) is a protein which is found on the surface of most prostate cancer cells, but not on healthy cells. Therefore, PSMA can be used to identify which cells are cancerous and which are healthy. It can even be attached to a radioactive molecule, called lutetium- 177 (¹⁷⁷Lu), to guide it directly to the cancer cells, without damaging healthy cells.

¹⁷⁷Lu-PSMA is injected into the bloodstream and the radioactive molecules are taken up inside the cancer cells where they shower them with DNA-damaging radiation. ¹⁷⁷Lu-PSMA can target multiple cancer sites at the same time so it can help those whose prostate cancer has spread to other places in the body.

¹⁷⁷Lu-PSMA is becoming more and more available in the UK and could treat many patients with fewer side-effects than standard radiotherapy. However, it does not work for all patients at the moment.

The researchers will combine ¹⁷⁷Lu-PSMA with drugs that will increase the amount of DNA damage to cancer cells. For example, they will test drugs that stop the cancer cells from being able to repair themselves. This should improve the efficacy of ¹⁷⁷Lu-PSMA so that it will work better and for more prostate cancer patients leading to higher survival rates. They will be testing ¹⁷⁷Lu-PSMA with approximately 1,000 different drugs in the hope of finding a successful combination.

This project is still in the early stages but the researchers have begun to test different drug combinations with ¹⁷⁷Lu-PSMA.  In the next stage of their research, the researchers will use SPECT imaging to measure the DNA damage following treatment with ¹⁷⁷Lu-PSMA. This will enable them to see how effective this type of radiotherapy is at treating prostate cancer. They hope to find successful combinations that could lead to clinical trials and eventually improved and personalised radiotherapy treatment for prostate cancer patients.

This project is a collaboration between researchers and clinicians from the University of Oxford and the Oxford University Hospitals Trust. They will also be collaborating with a researcher from the Erasmus University Medical Centre in the Netherlands.