Revolutionary tailor-made cancer treatment for patients

A pioneering cancer research project may finally be overcoming an issue that has plagued scientists for over 40 years. Laszlo Szekely, Professor of Haematological Malignancies at the Karolinska Institute in Stockholm, thinks he may have developed a research technique that will transform drug treatment for tumours by bringing patient-specific testing to the front line.

“The greatest paradox of cancer therapy,” says Laszlo Szekely, Professor of Haematological Malignancies at the Karolinska Institutet in Stockholm, “ is that an optimal treatment should be evidence based and individualised at the same time.”

Solving this paradox forms the basis of a ground-breaking research project into personalised drug treatment for cancer. The project aims to tailor the process of patient care to such an extent that each cancer patient can be offered individual testing by their oncologist, to identify the most effective combination and concentrations of drugs for that patient.

“Each patient is different,” explains Professor Szekely of his approach. “Just because they may have a similar form of cancer, at a similar stage, to other patients does not mean they will react in the same way, to the same drugs – and of course each may have other medical complications we have to take into account. Yet until now we have had to use a homogenised approach to drug treatment because we have not had the technology to make it feasible to treat each case individually.”

Personalised drug selection is an idea that was first mooted over 40 years ago, but the sheer scale of the task ensured it remained a pipe dream – until now. “There are more than 100 cancer drugs available, with new ones being approved all the time,” says Professor Szekely. “There are over 200 cancer types, each with numerous sub-groups, resulting in well over 1000 different biological entities. Then imagine trying to test each different concentration of each drug on each entity, and you have an impossibly large number of combinations to deal with under the current strategy of drug selection.”

But new technology, developed by Professor Szekely and his team over the last five years, is enabling that choice to be far more selective. “Unlike the classical method, he explains, “ours is based on culturing free-floating tumour cells outside the body, with cells taken from blood, or from fluid that builds up in the body due to cancer. The cells are tested on prefabricated plastic plates that harbor 384 separate wells.

The plates are prepared by the Biomek 2000 fluid-handling robot, which can prepare hundreds of plates at a time, much faster and without the potential for human error.”

Professor Szekely has also developed a fluorescence staining technique so tumour cells killed by a drug and those resistant to it show up in different colours. Supporting this are state-of the-art microscopes and high resolution imaging equipment along with cutting-edge computer software to analyse and present results.

Along with the availability of new technologies, it’s the dramatic fall in the cost of such technology that has made the devices viable, he says. “For example, many components, such as microchips, are now a tenth or even a hundredth of the price they used to be, thanks to mass production for the telecoms industry and so on.

This not only makes it more affordable for us to build such equipment, it will make it affordable for other testing centres to have them once they are in production – devices that are practically absent from routine clinical laboratories today because of the prohibitive cost.”

As well as the increased accuracy of the new technique, it is also extremely versatile – and the time savings are staggering. “Our system can routinely determine the drug sensitivity pattern for 30, 60 or 90 drugs, on 2-6 million malignant cells in 3 days,’ says Professor Szekely. We can test combinations of drugs, we can test different concentrations of the same drug, we can test young and mature carcinomas, and the external testing method means it can even be used for paediatric patients.”

Professor Szekely is focusing his research on around 300 leukemia and lymphoma patients as well as on patients with late-stage carcinomas,. Many of these patients have been in remission but seen tumours come back repeatedly. “We’re looking at each patient and saying – why are these tumours so resistant? Which drugs, at which concentration, are needed to kill them off, rather than just suppressing them?” he says.

So far, results have been promising. “We have analysed the sensitivity pattern of over 260 live tumour samples and can draw three important conclusions,” he says. “Firstly that there are no wonder drugs – which further emphasises the need for an individualised approach; secondly that all of the currently approved drugs can at least be effective against some tumours; and finally that even very resistant tumours can still be sensitive to a few drugs. In fact, we found only five tumours out of the 260 we tested that showed resistance to all 30 drugs we used.”

Professor Szekely sees another benefit in the fact that he is testing the tumours only with approved drugs, or those due to be approved. “This isn’t about finding new wonder drugs – I think our research suggests they don’t exist,” he says.

“But if we can establish which of the approved drugs are right for a particular patient, as part of their standard treatment, then we have a drug we can use straight away, without the need for the expensive, time-consuming testing process that trial drugs would require. It’s a very efficient method.”

Thanks to an innovative approach and the realisation that technology has reached a level where it can play a central role in research, Professor Szekely is turning four decades of cancer treatment on its head.

Instead of matching the patient to the drugs, it’s now about matching the drugs to the patient. “One might assume at first that an individualised approach would be far more costly and time consuming than the current practice, but our research proves just the opposite is true,” he says.

“I believe this tailored treatment can be applied successfully to other cancers, and even to bacterial diseases – something which others are working on right here at the Karolinska Institutet. I’d like to think we have found a way forward.”

Click here to access the project website.

Published: Monday, 10th October 2011