Scientists found the technique – known as nuclear magnetic resonance (NMR) – was able to predict at an early stage how a brain tumour called a glioma was responding to treatment with the drug temozolomide.
The team of researchers, funded by Cancer Research UK and the Medical Research Council, at The Institute of Cancer Research, developed the scan from a machine widely used to identify molecules in chemistry laboratories.
They studied temozolomide – a chemotherapy drug developed by Cancer Research UK which works by causing lethal DNA damage in cancer cells. It is licensed in the UK for use against gliomas that have returned since first being treated.
Doctors currently learn whether or not the drug is proving effective in a patient by monitoring the size of tumours after months of treatment. Now researchers have found they could get this information much more quickly by using a sophisticated machine to monitor subtle chemical changes in tumours brought about by temozolomide.
Study author Dr Andrzej Dzik-Jurasz, Honorary Senior Lecturer at The Institute of Cancer Research, explains: “NMR has been used in laboratories for over 40 years to determine the chemical structure of molecules. Although the technique has been used in cancer research for a number of years, this is the first attempt to use it to monitor the action of a drug within a low-grade brain tumour.”
“We set out to see if we could use NMR to monitor the effect of temozolomide on tumours in people. Excitingly, we were able to identify chemical changes using the machine which were early indicators that the drug was working.
The group used the NMR machine to measure the amount of a molecule called choline in the tumour. The presence of choline in cells may indicate that the cells are dividing and hence that a tumour is growing. An alteration in the choline signature during anti-cancer treatment can suggest that the drug is having an effect on the tumour.
The team tested the theory by monitoring two indicators in patients receiving temozolomide as treatment for their brain tumours. They measured both the amount of choline in a tumour using NMR and the size of the tumour using magnetic resonance imaging (MRI).
Results from each test correlated, indicating that monitoring choline in a tumour is a good early indicator of whether or not temozolomide is halting cell metabolism and tumour growth.
Fellow author Professor Martin Leach, of the Cancer Research UK Clinical Magnetic Resonance Research Group at The Institute of Cancer Research, says: “Our results tell us that using NMR could give doctors an early indication of whether temozolomide is working or if a patient could benefit more by switching to another drug.
“NMR could help doctors identify different types of gliomas and learn about their interactions with drugs by looking directly at cancer cell behaviour. They could then predict which tumour types are likely to respond to treatments before giving them to patients.”
Professor Robert Souhami, Cancer Research UK’s Director of Clinical and External Affairs, says: “It is often very difficult to tell when giving a drug to a patient if they are likely to benefit from it. The team have found a way to potentially get an early and extremely useful indication using existing technology in a new context.
“Many useful drugs have been developed against cancer, but not every drug works in all patients. We hope that developments in this area of research will help target treatments to those patients who are most likely to benefit from them.”
- British Journal of Cancer90 (4)
Temozolomide (Temodal) is used to treat certain brain tumours. It is type of drug known as an alkylating agent and was developed by Cancer Research UK. It works by stopping cancer cells from making new DNA. If they cannot make DNA, they can’t divide into two new cancer cells.
Unlike most chemotherapy drugs, temozolomide can cross from the blood into the brain.
Temozolomide is used to treat glioblastoma that has come back since first being treated. Glioblastoma is the most common form of primary brain tumour.
The researchers evaluated temozolomide as a primary treatment following surgery in patients with low-grade gliomas. Low grade gliomas tend to be slow-growing tumours, and respond better to chemotherapy treatment than high-grade tumours.
The Medical Research Council (MRC) is a national organisation funded by the UK tax-payer. Its business is medical research aimed at improving human health; everyone stands to benefit from the outputs. The research it supports and the scientists it trains meet the needs of the health services, the pharmaceutical and other health-related industries and the academic world. MRC has funded work which has led to some of the most significant discoveries and achievements in medicine in the UK. About half of the MRC’s expenditure of £430 million is invested in its 40 Institutes, Units and Centres, where it employs its own research staff. The remaining half goes in the form of grant support and training awards to individuals and teams in universities and medical schools.