A scanning electron microscope image of a breast cancer cell
IF RESEARCHERS could identify what it is that makes a tissue tumorous, they might be able to develop drugs aimed precisely at the cause of the cancer. At present, they know that certain molecules become active in tumours found in certain parts of the body. Both head-and-neck cancers and breast cancers, for example, have an abundance of molecules called epidermal growth-factor receptors (EGFRs). Now one group of researchers has developed a technique that could, in the long term, diagnose almost all cancers according to their molecular origin rather than what part of the body they had cropped up in. That might eventually allow doctors to apply more relevant treatment. Moreover, in the short term, the new technique can already reveal how advanced a person's cancer is, and thus how likely it is to return after treatment.
At present, pathologists assess how advanced a cancer is by taking a sample, known as a biopsy, and examining the concentration within it of specific receptors, such as EGFRs, that are known to help cancers spread. Peter Parker of Cancer Research UK'sLondon Research Institute had the idea of employing a technique called fluorescence resonance-energy transfer (FRET), which is used to study interactions between individual protein molecules, to see if he could find out not only how many receptors there are in a biopsy but also how active they are.
The technique uses two types of antibody, each attached to a fluorescent dye molecule. Each of the two types is selected to fuse with a different part of an EGFR molecule, but one will do so only when the receptor has become active.
Pointing a laser at the sample causes the first dye to become excited and emit energy. With an activated receptor, the second dye will be attached nearby and so will absorb some of the energy given off by the first. Measuring how much energy is transferred between the two dyes indicates the activity of the receptors.
Dr Parker's idea was implemented by his colleague Banafshe Larijani. She and her colleagues used FRET to measure the activity of receptors in 122 head-and-neck cancers. They found that the higher the activity of the receptors they examined, the more likely it was the cancers would return quickly following treatment. The technique was found to be a better prognostic tool than conventional visual analysis of receptor density. Dr Larijani believes the technique could help to provide more personalised cancer diagnosis and treatment within three years.
To that end, engineers in the same group have now created an instrument that automates the analysis of samples. Tumour biopsies are placed on a microscope slide and stained with antibodies. The system then points the laser at the samples, records images of the resulting energy transfer and interprets those images to provide FRET scores. These scores help doctors diagnose the type and progress of a tumour. Results are available in as little as an hour, compared with four or five days using standard methods.
Having established the principle with head-and-neck cancer, the team are now trying to extend it. In September they will begin work on a large-scale trial to see whether FRET can accurately “hindcast” the clinical outcomes associated with 2,000 breast-cancer biopsies. Moreover, if patterns of receptor-activation for other types of cancers can be characterised, the technique might be applied to all solid tumours (ie, cancers other than leukaemias and lymphomas). The team are now trying to identify which other receptors could be used in this way.
If they succeed, it will be grist to the mill of all those researchers who want to switch from classifying cancers anatomically to classifying them biochemically. Most cancer specialists think that patients with tumours in different parts of the body that are triggered by the same genetic mutations may have more in common than those whose tumours are in the same organ but have been caused by different mutations. The approach taken by Drs Parker and Larijani could lead to a way of making such classification routine. That could, in turn, create a new generation of well-aimed therapies and allow doctors to decide which patients should receive them in which combinations and which doses.