PG12-12 Mairs Lay summary
Principal Investigator: Dr Rob Mairs, Group Leader at the CRUK Beatson
Laboratories in the Institute of Cancer Sciences, University of Glasgow
Lay title:
Improving radiation treatment of prostate cancer
What are you proposing?
Recently we have developed a small molecule with a radioactive label (radiolabelled), [131I]Trofex, which
selectively binds to a prostate-specific marker (PSMA) expressed on prostate cancer cells that have spread
(metastatic). This radiopharmaceutical (radiolabelled drug) has anti-tumour activity as a single agent.
However, it is likely that its effectiveness will be significantly enhanced by combination with other drugs acting
as radiosensitisers (making cancer cells more sensitive to radiation therapy). We propose to evaluate
radiosensitisers in combination with the PSMA-specific radiopharmaceutical in order to determine the most
effective schedules of therapeutic agents which enhance killing of tumour cells while minimising side effects.
Why are you proposing it?
Although radiotherapy is widely used in the clinical management of prostate cancer patients, damage to
neighbouring normal organs limits the radiation dose which can be delivered. Significantly, there is no curative
treatment for prostate cancer that has spread. Targeted radiotherapy using [131I]Trofex, a PSMA-specific, small
molecular weight radiopharmaceutical, enables the delivery of radiation selectively to cancerous sites while not
harming normal tissue. The combination of this targeted approach with the administration of radiosensitisers is
expected to provide the optimal treatment for patients with prostate cancer that has spread.
How are you proposing to do it?
Using prostate cancer cell lines as models, we intend to determine the interaction between [131I]Trofex and
radiosensiters. These agents target various pathways which help resistance to radiation-induced cell death.
Combinations of drugs and radiopharmaceuticals that interact well will be further evaluated in a threedimensional in vitro model (i.e. not in cells) of metastatic prostate cancer and in human tumour tissue grafts in
immune deficient mice.
How long will it take?
The time required is three years.
What is the budget?
£204,590.05
What are the expected outcomes?
Having established the most effective combination strategies in laboratory models, we will, in association with
our clinical collaborators, design clinical trials based on the administration of radiosensitisers with [ 131I]Trofex
and using appropriate scheduling, dosing and controls.
Prostate Cancer UK is a registered charity in England and Wales (1005541) and in Scotland (SC039332). A company limited by guarantee registered number 2653887 (England and Wales).
How could it make a difference to the lives of men affected by prostate
cancer?
Targeted radiotherapy using [131I]Trofex offers, for the first time, an effective treatment of metastatic prostate
cancer. The radiopharmaceutical used in this study is more specific than current treatments and will result in
patients’ being exposed to lower doses of radiation and reduced risk of normal tissue damage. Clinical trials
will involve the most effective radiosensitising drugs, scheduled in combination with the radiopharmaceutical to
give maximal anti-tumour effect with minimal side-effects.
Please write a summary of the project in one sentence only.
We will evaluate the ability of drugs to enhance the sensitivity of prostate cancer cells to a prostate cancerspecific radiopharmaceutical in order to determine the most effective schedules of administration which will
then be used as a basis for designing clinical trials.