Established by Bengt Sjöberg 2016
In addition to the Sjöberg Prize, where 9/10 of the prize money is reserved for research purposes, the Sjöberg Foundation has in 2018 made decisions on grants totaling approximately SEK 59 millions. This sum includes SEK 9 millions for continuation of the project initiated in 2017 concerning the national network for cancer research and uniform patient reviews for the whole country, see: Grants 2017, National collection of valuable data from cancer care.
Can mistletoe extract be beneficial in pancreatic cancer?
Mistletoe extract has been used to treat cancer in complementary medicine for almost a century. To find out whether the substance really works, researchers are now testing its effect in a large clinical study, in which 290 people with incurable pancreatic cancer will participate. The Sjöberg Foundation is providing SEK 4.5 million of funding for the project, which is expected to finish in 2021.
Almost half of all Europeans who get cancer try to manage their disease with the help of herbal medicines as a complement to conventional treatments. One of the most used herbal medicines is the extract from the European mistletoe (Viscum album L).
Cell and animal trials have demonstrated that mistletoe extract inhibits the growth and spread of cancer cells, and a boost to the immune system has been seen in studies on humans. However, its effect on survival and quality of life in incurable cancer remains uncertain. Researchers have carried out many studies, but many are of relatively low quality and few have examined the impact on length of life.
Since 2016, to eradicate the uncertainties about the effects of mistletoe extract on incurable cancer, researchers at various Swedish universities have been conducting a clinical study called MISTRAL. It will include a total of 290 people with pancreatic cancer, of whom half will receive mistletoe extract and half a placebo. The study is of high scientific quality and its primary aim is to investigate whether mistletoe extract can extend the life of patients, as well as whether it can improve quality of life by counteracting nausea, tiredness, pain, weight loss and other difficult symptoms of the disease. In two ancillary studies, researchers will also map the molecular mechanisms behind any effects of mistletoe extract, and investigate whether any subgroup of patients responds better to the extract than others.
New form of immunotherapy for hard-to-treat cancer
Immunotherapies – treatments where the body’s immune system targets cancer tumours – can, in some cases, eradicate metastatic cancer, but have no effect on other cases. Olle Korsgren and his colleagues are developing a new form of immunotherapy that will hopefully help the body’s immune system to identify and attack types of cancer that are more difficult to treat.
For immunotherapy to work, the immune system must be activated and identify the cancer cells as alien to the body. Once this happens, the immune system makes a ruthless attack and, in many cases, eradicates all the cancer cells from the body.
Unfortunately, some tumours, including pancreatic cancer, are able to hide from the immune system and immunotherapy has little effect. Olle Korsgren, professor of transplantation immunology at Uppsala University, and his colleagues have received SEK 4 million from the Sjöberg Foundation to develop a new form of immunotherapy. Using methods from molecular biology, they have constructed an oncolytic virus, which selectively kills cancer cells by exploding them. The virus also carries the genetic code for two molecules that wake the body’s immune system. One is an enzyme that decorates cancer cells’ proteins with a kind of molecular signalling flag, so that the immune system can identify them as exogenous. The other molecule helps to activate the immune system’s aggressive killer cells.
Thanks to its clever construction, the virus can trigger the dozing immune system and make it attack the tumours. The plan is that this new form of immunotherapy will be tested on people with pancreatic cancer no later than 2022 and the hope is that it will lead to treatment that saves lives. At a later stage, the treatment will also be tested on other forms of cancer.
Will undermine cancer cells’ defence against immunotherapies
Cancer cells never survive alone; instead, they are often helped by other cells in the body. Tumour-associated macrophages are one example, as they work to protect tumours in the pancreas from immunotherapies. Mikael Karlsson now aims to block these protective cells, so that immunotherapies will also be effective against pancreatic cancer.
In recent years, immunotherapies have revolutionised cancer care. By easing specific brakes on the body’s powerful immune system, researchers have succeeded in getting it to target tumours. In some cases, this leads to the immune system completely eradicating the cancer and curing the patient.
However, for pancreatic cancer, these new immunotherapies have been a disappointment. One reason is believed to be that tumours in the pancreas house special cells, known as tumour-associated macrophages, which inhibit the immune system and protect the tumour from the attack.
Mikael Karlsson, professor of immunology at Karolinska Institutet, has received SEK 6 million from the Sjöberg Foundation to find therapies that can weaken this protective barrier to immunotherapies. In animal trials, his research group has shown that antibodies that are designed to target tumour-associated macrophages make immunotherapy more effective. As a result of this new immunotherapy, the tumour grows more slowly and is less likely to spread.
Mikael Karlsson will now learn even more about these tumour-associated macrophages. How do they influence the disease prognosis? How do they protect the tumour from the immune system? And – most of all – is it possible to undermine this barrier in humans too, so that immunotherapies can have a better effect on pancreatic cancer?
Will knock out tumours’ resistance to treatment
New types of targeted therapies for lung cancer can initially make tumours shrink dramatically, but cancer cells often become resistant to treatment and start growing again. Simon Ekman will investigate whether it is possible to undermine the cancer cells’ resistance to targeted treatments, making them more effective.
Researchers have recently developed a number of targeted therapies for different types of lung cancer, which were initially very promising. However, after one or a few years, the tumours often become resistant to these therapies, which limits the patients’ survival.
Simon Ekman, oncologist and associate professor at the Department of Oncology-Pathology, Karolinska Institutet, has received SEK 4.5 million from the Sjöberg Foundation to try to knock out the tumours’ defences against targeted therapies. All cells have special molecules, miRNA, that govern which genes are active in the cell. Simon Ekman’s previous research has demonstrated that these miRNA molecules can orchestrate the cancer cells’ defences against targeted therapies.
He will systematically map which miRNA molecules are found in different types of cancer cells, in order to understand which of these cause resistance to specific therapies. In a second stage of the project he will knock out the miRNA molecules that protect the tumour, so that the targeted therapies can continue to work until the tumour is eradicated.
Will look for new treatments for pancreatic cancer
Last year, the Sjöberg Foundation provided funding for the development of a new type of research animal, the avatar mouse, which can be used to optimise cancer treatments. Peter Naredi will use these mice to find more effective forms of treatment for pancreatic cancer, which is the deadliest form of cancer.
The prognosis for people with the most common form of pancreatic cancer, pancreatic adenocarcinoma, is poor. Only 6 per cent are still alive after five years and there is a desperate lack of effective treatments. Immunotherapies – where the body’s immune system is used against the tumours – has had an almost miraculous effect on some other difficult to treat forms of cancer, but has been disappointing for pancreatic cancer.
Peter Naredi, professor of surgery at the University of Gothenburg, has received SEK 6 million from the Sjöberg Foundation to look for new treatments for pancreatic cancer. He will use a new type of experimental mice, avatar mice, in the project, as they can develop copies of real patients’ tumours. Using these, and cell cultures, he will see whether any existing pharmaceutical can counteract the cancer cells’ growth and whether it is possible to combine different pharmaceuticals to improve their effect.
He will also investigate whether it is possible to encourage the body’s immune system to attack cancer cells in the pancreas. This involves getting the immune system to recognise the cancer cells as something alien to the body. Using the genetic mutations carried by cancer cells as a basis, Peter Naredi will develop a vaccine that stimulates this process and hopefully allows immunotherapies to work. The long-term aim is to improve the treatment of pancreatic cancer so that more people can survive the disease.
Nordic evaluation of the best treatment for pancreatic cancer
Svein Olav Bratlie has been granted funding from the Sjöberg Foundation to run NorPACT-1, a large-scale Nordic study in which researchers evaluate whether it is better to use chemotherapy before or after surgery for pancreatic cancer. The study will also create a platform for future partnerships that can develop and improve the treatment of pancreatic cancer.
In cases where tumours in the pancreas are operable, patients usually undergo surgical treatment first and then receive chemotherapy. However, recent indications are that it may be better to do the opposite: of the patients who receive chemotherapy before the operation, more seem to be able to cope with the rough treatment, which can then be more effective.
To find out the order in which surgery and chemotherapy should be given, researchers at the university hospital in Oslo have initiated a major Nordic study, NorPACT-1 (Nordic PAncreatic Cancer Trial), which includes several Swedish universities. Svein Olav Bratlie, researcher at the Department of Clinical Sciences, the University of Gothenburg, will now receive SEK 3 million from the Sjöberg Foundation to lead, coordinate and run the Swedish part of the of the project. Thanks to this funding, the researchers will also have the opportunity to make detailed studies of tumours that have been surgically removed and investigate how chemotherapy affected them.
When the Nordic researchers create a platform for conducting NorPACT-1, they also lay a foundation for future cooperation. Large-scale international projects are often required to evaluate the effect of the various treatments on patients. Closer cooperation will also provide researchers with better opportunities to learn from each other to jointly develop knowledge in the area.
Towards better end-of-life care
There is no curative treatment for more than half of all people who get cancer of the oesophagus or stomach, and many die within a year of being diagnosed. Jimmie Kristensson will investigate how palliative care can be designed so that patients have the best possible quality of life.
Research shows that early access to palliative care – care given to people with life-threatening diseases – increases patients’ quality of life, lessens symptoms and may extend the life of someone with cancer. Despite this, it is often introduced at a late stage in the cancer’s progression and there are significant knowledge gaps regarding how it should be designed for the greatest possible benefit to patients and relatives.
Jimmie Kristensson, associate professor at the Department of Health Sciences, Lund University, has received SEK 2.7 million from the Sjöberg Foundation for the development of palliative care for patients with incurable oesophageal and stomach cancer. In the first phase of his work he will map out the care that these patients generally receive during their final stages of life. When is palliative care introduced? What help do patients and relatives feel that they need? How do they deal with the pain, anxiety, nausea and other experiences that affect quality of life? Jimmie Kristensson will also study what approach care staff take to palliative care. What prevents them from introducing palliative care earlier? How can this decision be influenced?
In the second phase, and in cooperation with patients, care staff and relatives, Jimmie Kristensson will develop a structure for the potential design of palliative care, so those affected receive the care, help and support they need. The aim is that the disease trajectory and the end of life will be as good as possible, for both patients and relatives.
How can pancreatic cancer be tackled more effectively?
Few people survive pancreatic cancer and there is an urgent need for new treatment methods. Karin Jirström will make detailed studies of how tumours in the pancreas evolve during chemotherapy and how the body’s immune system influences development. The aim is to be able to personalise treatment approaches to combat this deadly disease.
In recent years, researchers have developed innovative cancer therapies which, in some cases, can even cure metastatic disease. However, none of these new treatments have proven to be efficient against pancreatic cancer, which is a particularly aggressive type of cancer. The tumour has often spread when it is diagnosed and is then inoperable. Most patients are treated with chemotherapy, but only a few per cent are alive after five years.
Karin Jirström, professor of pathology at Lund University, has received SEK 4.5 million kronor from the Sjöberg Foundation to improve the treatment for pancreatic cancer. In a large-scale project, she will map tumours from around 150 patients and investigate how pancreatic cancer cells evolve during chemotherapy, and how this process is affected by the body’s immune response.
She will also look for biomarkers in the blood, which may indicate when a tumour is about to become resistant to chemotherapy and it is time to change treatment. The long-term aim is to develop more adaptive and individualised treatment strategies so that more people survive this devastating disease.
For better precision in lung cancer treatments
A number of new treatments for lung cancer have appeared in recent years. Maria Planck and Johan Staaf will develop methods that make it easier for doctors to decide which treatment will have the best effect on a tumour, as well as quickly discover whether the tumour is becoming resistant to treatment or if a relapse is about to occur.
Lung cancer is one of the most common causes of death, both in Sweden and the rest of the world. The disease is often diagnosed at a late stage and, even if treatment is initially effective, many patients eventually suffer a relapse.
The good news is that researchers have now developed a range of targeted treatments, which can extend the lives of patients. Also, immunotherapies – rewarded with the 2018 Nobel Prize in Physiology and Medicine – have demonstrated an almost miraculous effect on some types of lung cancer.
The challenge for the treating doctor is now to determine which of the various treatments will be most effective for a particular patient, and to quickly determine when a patient is about to suffer a relapse or when it is time to change the treatment because of resistance. Maria Planck and Johan Staaf, both associate professors at the Department of Clinical Sciences, Lund University, have received SEK 6 million from the Sjöberg Foundation to help doctors in this work. In their project, they will identify biomarkers that can predict which form of treatment will work best, or warn of developing resistance or a relapse. The aim is to be able to optimise treatment for each patient, to make it as efficient as possible.
Will weaken tumours’ supporting tissue
A tumour contains many different cell types. Most are cancer cells, others are healthy cells that have been hijacked and support the tumour as it grows. Kristian Pietras and Daniel Öhlund will study cancer-associated fibroblasts, which support tumours in the pancreas. The aim is to find a pharmaceutical that can stop fibroblasts functioning and thereby weaken the tumour.
The most common form of pancreatic cancer, pancreatic ductal adenocarcinoma, is one of the deadliest forms of cancer. The tumour will already have spread in four-fifths of people who are diagnosed, and no curative treatments are available.
Kristian Pietras, professor of molecular medicine at Lund University, and Daniel Öhlund, assistant professor of oncology, Umeå University, have received SEK 4.5 million from the Sjöberg Foundation for investigating a new way of attacking pancreatic tumours. They will study the supporting tissue, stroma, that surrounds the cancer cells. The stroma partly consists of connective tissue proteins, partly of cells called fibroblasts. These cells are actually healthy, but the cancer cells can control some fibroblasts by sending out signal substances to make them support the tumour. They can be made both to produce substances that drive cancer growth and also protect the tumour from the body’s immune system and from chemotherapy.
Other fibroblasts do not allow themselves to be controlled, and can actually counteract tumour growth. Kristian Pietras and Daniel Öhlund will study the various subgroups of fibroblasts and, in particular, become more familiar with the cancer-associated variants. The long-term aim is to find a weakness in them that can be attacked with pharmaceuticals. If the fibroblasts are eliminated, the tumour will be weakened and may be more susceptible to existing treatments.
Can exhaled air be used to diagnose lung cancer?
In order to diagnose and treat lung cancer, it is often necessary for a doctor to take a tissue sample from the lung. Sandra Lindstedt Ingemansson will investigate whether it is instead possible to diagnose lung cancer by analysing particles in exhaled air. One aim is to be able to find small tumours, so that treatment can start at an earlier stage of the disease.
Lung cancer is the fifth most common form of cancer in Sweden, with over three thousand people getting it every year. When doctors diagnose the disease, they often start by taking an X-ray. A bronchoscopy is then performed, in which a flexible tube with fibre optics is fed into the lung so that the doctor can study the tissue. A tissue sample is often taken to decide which treatment should be used, using a needle that is stuck into the tumour.
The various types of examination that are necessary to diagnose and treat lung cancer are often unpleasant for the patient, as well as entailing some risks. Sandra Lindstedt Ingemansson, associate professor of thorax surgery, Lund University, has received SEK 4.5 million from the Sjöberg Foundation to discover whether it is instead possible to discover tumours by analysing the patients’ exhaled air. When we breathe out, nanoparticles and microparticles from the lung tissue travel with the air and these particles may reveal whether or not a tumour is beginning to develop.
A sample using exhaled air is much easier for a patient to supply than a tissue sample. The hope is also that this new diagnosis method will be more sensitive, making it possible to find smaller tumours and more quickly discover when they are developing resistance to a particular treatment. The earlier an effective treatment can begin, the greater the chance of the patient surviving the disease.
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