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Pinpoint cancer treatment

Richard Rosenquist Brandell is both a researcher and a physician specialising in clinical genetics and he works in close collaboration with cancer care.

Knowledge of the genetics underlying cancer and which patients respond well to various treatments is expanding. In Uppsala, work is being done to help develop treatments which are more adapted to individuals and methods for making earlier diagnoses. “It requires close collaboration between researchers and clinics,” says Tobias Sjöblom.

He is a researcher at the Department of Immunology, Genetics and Pathology at the Rudbeck Laboratory in Uppsala. Here, research is being carried out into several of the most common cancer diagnoses such as breast cancer, colon cancer and leukaemia.

For the last five years, samples have been collected from cancer patients with nine different cancer diagnoses before, during and after treatment as part of the strategic U-Can programme. It is an excellent basis for the research according to Tobias Sjöblom:

“What is unique about U-Can is that we monitor the patients throughout their treatment. There are plenty of biobanks with samples from when the patients were given their diagnosis but we continue to collect samples from every patient, which makes sense.”

Things have gone well. Among the reasons for this are the research nurses “who keep a very close eye on their patients”, and the skilful pathologists. But collaboration has also been needed between various hospital departments and the researchers at the Rudbeck Laboratory.

When a patient is treated for cancer, a number of different specialisations are involved: oncology, surgery, pathology, radiology… Building up a collection from one particular diagnosis requires that around ten people need to agree on how the samples are to be collected. This has meant long discussions about who is to do what and who is going to pay for it. But it is worth it, according to Tobias Sjöblom.

“We have hit upon a good model for doing this which very few others in the world have – a way to involve large sections of the care chain. Our total has now passed 8 500 patients from whom we have collected samples and we can now start to reap the harvest.”

One of the researchers who uses U-Can is professor Richard Rosenquist Brandell. He is doing research into a form of leukaemia, chronic lymphocytic leukaemia (CLL). This is an incurable cancer where some patients can live without symptoms for many years even without treatment. In other patients, the course of the disease is more aggressive they relapse more quickly despite new medication.

Richard Rosenquist Brandell and his research team recently discovered a gene which may be connected with relapses after treatment.

“Our study is one of the first to examine a homogenous group of patients who have all undergone the same treatment and have had a relapse within an average of two years. Many of these, we discovered, had mutations in the same gene. In most cases, the mutation was there before treatment was started.”

In addition to being a researcher, Richard Rosenquist Brandell is also a physician specialising in clinical genetics and he co-operates closely with cancer care. Close collaboration between the university and the hospital has led to a facility for clinical genetic testing being set up at SciLifeLab. Its aim is to apply new technology to current diagnostics for cancer, leukaemia and hereditary diseases.

“If in the past we looked for three genes in a leukaemia patient, we can now look for 50 genes for the same cost. We have both completely new opportunities for treatment and for improved diagnostics. It is a combination which bodes well for the future.”

He shows me a panel – or map – of genes used to find the most important genetic abnormalities. This information can then be used to determine which type of treatment the patient receives.

“We see which abnormalities the patient has at molecular level and so we can group the patients into high, medium or low risk.”

Doctors and molecular biologists work closely together to ensure that such knowledge gets to where it is needed – the health service and the patients.

“We print the results and interpret them for the doctors at the clinics. The results are quite complicated, after all. We put a lot of energy into explaining them and this makes for a useful dialogue.”

Experts in bioinformatics and bioethics are needed in order to deal with all the genetic information. But both researchers and doctors can make use of the knowledge, according to Richard Rosenquist Brandell. He sees before him an explosion of new knowledge in the next few years.

“As a geneticist I think it is a very exciting time.”

There is another major unexplored area for U-Can. With such a large collection of samples from a number of different cancer types, it is possible to search for biomarkers for cancer. Such knowledge could lead to earlier discovery and improve survival rates.

“We have a collection which looks into the future. It includes more or less every patient in a certain geographical area with certain illnesses. At the same time, other cohort studies are in progress in the same area which also encompass a large proportion of the population. It is a very good starting point for biomarker development,” says Tobias Sjöblom.

At present, a major project is being planned jointly by Umeå University and Uppsala University to try to find a systematic way to develop biomarkers for the early discovery of cancer in different patient groups.

“This is something which has previously been very difficult to do. Much of the difficulty has been the lack of access to patient cohorts grouped together in an optimum manner for this purpose. But now we have them. There are not many around the world who have our breadth of diagnoses.”

Developing tests for the early discovery of cancer does not just mean the early discovery of the preliminary stage of cancer. One has to know which organ is affected. Otherwise, the result will just cause anxiety for the patient and the health professionals can do nothing about it. These kinds of analyses must therefore be carried out in parallel for many different cancer diagnoses so that it is possible to pinpoint what is distinctive for different kinds of cancer.

Why is it so important that cancer is discovered in time?

“Early discovery is the best cure for cancer I usually say. If, for example, you discover intestinal cancer early it may be possible to cure it using a simple surgical procedure, especially if the tumour has not had time to spread. If you could discover any potential tumours only a few years earlier, it would greatly increase the chance of survival.”

As the programme coordinator for U-Can, he wants to press on with development and take the step from mostly collection to collection with a greater focus upon the research to be done.

“There is window of opportunity to take and that window is open now. We have put together a fine collection here, very elaborate and of high technical quality. This now has to be given research value,” says Tobias Sjöblom.

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FACTS: U-Can

Run collaboratively by Uppsala University, Umeå University, Stockholm University and KTH (the Royal Institute of Technology, Stockholm).

Collects and organises samples taken from patients before, during and after cancer treatment. Information about the patients and X-ray images are also collected.

To date, more than 8 500 patients have been included, diagnosed with colorectal cancer, haematological neoplasms, lymphoma, prostate cancer, brain tumours, gynaecologic cancer, neuroendocrine tumours, breast cancer and lung cancer.

The material is used for:

  • developing improved diagnostics and better characterisation of various cancer types
  • developing and evaluating new medication and other new treatment methods
  • examining what makes a treatment work or not

2016-04-26