Established by Bengt Sjöberg 2016
National collection of valuable data from cancer care
The more data a researcher has available, the more they can learn. For many cancer researchers, the national network for samples and data collected in cancer care that the Sjöberg Foundation is building is thus a dream come true. Its long-term aims include better precision in cancer treatment and to make it easier for doctors to follow the development of cancer in individual patients.
All over Sweden, every day, thousands of samples are taken from cancer patients to diagnose disease, design treatment and evaluate its results. All this data is invaluable to cancer researchers, but the various test results end up in different county councils’ record systems, which are often structured in completely different ways; some important information is found in the running text in patient records and some details are never registered. A researcher who wonders what effect a particular combination of pharmaceuticals has on a particular type of tumour may therefore need to spend months or years searching for the data necessary to find the answer, if it’s even possible.
Instead, to make the treasure trove of information generated every day by Swedish cancer care easily available to researchers, the Sjöberg Foundation is forming a national network for research using samples and data from cancer care. The network is preliminarily called the Partnership for Precision Medicine in Cancer. The ambition is that samples and data from cancer patients, who have given permission for inclusion in the project, will be collected and stored in a structured manner by participating county councils. This information will then be available to physicians and researchers who will, for example, be able to evaluate the long-term efficacy and side effects of various treatments.
“This will boost Swedish oncology care and research, which will be able to access high-quality data sources,” says Tobias Sjöblom, cancer researcher and professor at Uppsala University, who is leading the project.
The Sjöberg Foundation provided SEK 8,870,000 in project funding in 2017.
Mapping a promising treatment for lung cancer
A new form of cancer treatment – checkpoint blockade – has brought about a revolution in the care of metastatic malignant melanoma. It also appears to hold promise for lung cancer, but not all patients benefit. Klas Kärre and Patrick Micke will map out why the treatment has different effects in different people. The hope is to improve the treatment so more people recover.
There are different types of killer cells in the body – such as cytotoxic T-cells – which are tasked with destroying abnormal cells, such as those that have been infected by a virus. Killer cells are extremely aggressive, but are held in check by a type of molecular brake so they don’t go berserk and damage healthy cells. As long as this brake is on, the killer cells stay calm.
In order to activate killer cells in cases of cancer, researchers have developed a treatment called checkpoint blockade, which releases the killer cells’ molecular brake and lets them loose in the body. The killer cells than attack the cancer cells. Data from clinical trials on metastatic lung cancer – which was once a death sentence – shows that up to 25 per cent of patients respond to this treatment. Both the primary tumour and the secondary tumours reduce in size and may, in some cases, entirely disappear.
However, the majority of the patients who are treated do not benefit and in around 20 per cent of cases the killer cells start to attack healthy cells in the body. This leads to severe side effects, similar to autoimmune diseases. Klas Kärre, Professor of Molecular Immunology at Karolinska Institutet, and Patrick Micke, Senior Lecturer at the Department of Immunology, Genetics and Pathology, Uppsala University, will follow up patients who receive checkpoint blockade for non-small cell lung cancer in Stockholm and Uppsala. They will map everything from gene expression in the patients’ tumour tissue to the way numerous different cells in the immune system react to the treatment, to better understand why some people become tumour-free while others get sicker.
One long-term aim is to discover methods for predicting which patients will respond to treatment, so that no one unnecessarily suffers severe side effects. There is also hope that the project will generate knowledge about how checkpoint blockade can be developed, so more people benefit from the treatment and recover.
Klas Kärre, Karolinska Institutet, and Patrick Micke, University of Uppsala, have received SEK 12,000,000 for the project, allocated over three years.
How do antioxidants make cancer cells metastasize?
In 2014, when Martin Bergö demonstrated that antioxidants stimulate cancer cells to grow and metastasize in mice, the news spread around the world and many people questioned whether his research was actually correct. He is now conducting detailed studies of how antioxidants change the metabolism of cancer cells, in the hope of developing new forms of treatment.
Antioxidants in fruit and vegetables have long been celebrated as real health-boosters; they strengthen the immune system, reduce inflammation in the body and protect against cancer. It thus came as a shock to many people when Martin Bergö, professor of Molecular Medicine at Karolinska Institutet, discovered that antioxidants appear to encourage the growth and metastasis of lung cancer and malignant melanoma in mice.
Initially, this new discovery was met with deep scepticism, particularly from the vast industry that sells antioxidants as dietary supplements. However, a number of independent research groups have now confirmed the finding that antioxidants may exacerbate the development of cancer, using cell cultures and animal experiments. These new insights may also explain the unexpected results of large-scale clinical trials in the 1980s and 1990s, in which researchers tried to prevent cancer by providing antioxidants as supplements, but where the trial subjects were instead more likely to get cancer.
To better understand why otherwise beneficial substances such as vitamin E-vitamin and beta-carotene have a negative effect on cancer cases, Martin Bergö is now mapping how they affect the cancer cells. Preliminary data indicates that they stimulate the production of a special protein which, in turn, affects the cancer cells’ metabolism so that they find it easier to grow and spread. The hope is that more knowledge about how this works could be used to develop new anti-cancer strategies, both as dietary advice and pharmaceuticals.
Martin Bergö has received a project grant of SEK 6,000,000 allocated over three years.
Towards improved treatment for aggressive lung cancer
Every year, around 300 people in Sweden get a specific form of lung cancer called ALK-positive. This is an aggressive form of cancer that often affects young people, many of whom have never smoked. Bengt Hallberg is conducting detailed studies of the ALK protein to better understand how its abnormal activity can be switched off, so more patients can survive the disease.
In ALK-positive lung cancer, the cells carry a genetic mutation that erroneously activates the ALK protein in the lungs. In turn, ALK stimulates the cancer cells’ growth; the tumours generally become aggressive and spread easily.
In order to help more people survive the disease, researchers have developed different pharmaceuticals that block the effect of ALK. These pharmaceuticals initially make the tumours shrink, but after two or three years the cancer cells usually become resistant to the treatment. The patient can then swap to the next pharmaceutical, which controls the tumour for a few more years, but many people die once the tumour spreads to the brain.
Bengt Hallberg, cancer researcher and professor of medical chemistry at the University of Gothenburg, is studying the ALK protein in detail to better understand how it functions and why it develops resistance. So far, researchers have found eleven different mutations in the protein that make the pharmaceuticals less effective. Bengt Hallberg is developing methods to map these changes in individual patients, so when a patient starts developing resistance to a specific pharmaceutical they can quickly be switched onto a more effective one. He is also investigating how they can be combined to be more potent; his long-term aim is to add more substances to the arsenal of pharmaceuticals for combatting ALK-positive lung cancer. The more pharmaceuticals are available, the longer the time that physicians can control tumour growth.
Bengt Hallberg has received a project grant of SEK 6,000,000 allocated over three years.
A successful model for testing cancer treatments
Researchers are using avatar mice – an innovative form of laboratory animal – to study tumours that are, in principle, exact copies of the ones in sick patients. Jonas Nilsson’s research on avatar mice is world-leading, generating knowledge that has been critical to the treatment of malignant melanoma. He will now investigate whether it is possible to develop avatar mice to study other problematic types of cancer, including lung cancer.
Researchers have long been able to study cancer in mice, but their tumours have often been a relatively poor copy of human cancers. Avatar mice, or patient-derived xenograft mice (PDX), have become important because, in them, it is possible to study tumours that are very similar to those in humans. Cancer cells from affected people are transplanted beneath the skin of the mouse, which then develops the same tumour as the patient. Using these mice, researchers have been able to test and optimise different pharmaceutical treatments for cancer.
As yet, avatar mice are the best experimental models for cancer that researchers have had, but when it comes to studying the latest weapon against cancer – immunotherapies – they have been unusable. In immunotherapies, researchers activate cells from the body’s own immune system, which then attack the tumours. It has been impossible to get these cells to survive in avatar mice but, in 2017, a research group run by Jonas Nilsson, Professor of Experimental Cancer Surgery at the Sahlgrenska Cancer Center in Gothenburg, succeeded in making these immune cells thrive in the avatar mice; this was a huge breakthrough.
Since then, Jonas Nilsson has used avatar mice to study immunotherapies combined with other treatments for malignant melanoma. This research is still in its early stages, but his research group has already been able to provide oncologists and surgeons with knowledge that has been decisive for the treatment of patients with spread malignant melanoma. The aim is now to investigate whether it is possible to produce avatar mice for studying and optimising the treatment of lung cancer, pancreatic cancer and bowel cancer, among others, with equal success.
Jonas Nilsson has received a project grant of SEK 6,000,000 allocated over three years.
Towards a tailored treatment for lung cancer
In Sweden, lung cancer is the type of cancer that takes most lives. To improve survival rates, Mattias Magnusson, Lund University, will isolate and study cancer stem cells from lung tumours. These stem cells are suspected of being the reason for the high level of mortality in cases where the disease relapses. One long-term aim is to find treatments that eradicate all cancer cells, even the difficult to deal with cancer stem cells.
People who get cancer are often treated with chemotherapy, which kills cells in the body that grow quickly. Every year, chemotherapy saves many lives but, relatively often, cancer cells become resistant to the treatment and patients have dangerous relapses. Researchers don’t know why this is the case, but one theory is that cancer stem cells, which drive cancer growth, survive the chemotherapy.
To better understand how lung cancer stem cells work, Mattias Magnusson, associate professor in molecular medicine at Lund University, will isolate cancer stem cells from the tumour tissue of lung cancer patients and map them in the tiniest detail. He will also expose cancer cells and cancer stem cells to different forms of pharmaceuticals in the laboratory, to see which eradicates them most effectively.
The long-term aim is that every lung cancer patient will be able to have a personally developed combination of pharmaceuticals. If the treatment also destroys cancer stem cells, it is likely that fewer patients will suffer relapses and more people will survive the disease.
To conduct this project, Mattias Magnusson has received SEK 6,000,000 allocated over three years.
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