Areas and methods in cancer and hematology research
Karolinska Institutet is at the forefront of cancer research in the world. The primary goal of the research conducted at KI is to make sure that as few people as possible suffer or die from cancer. Its research encompasses all areas, from the examination of molecules to the study of large demographic groups.
Roughly one third of the Swedish population develop cancer. There are several factors behind the increased risk of certain strains of cancer, such as dietary habits, smoking, hormone therapy, virus infections, genes and so on. Yet the researchers still need to find out much more about how cancer forms. There are long-term studies of how diet, genes and other environmental factors influence the risk of cancer and molecular research designed to find out why a normal cell changes into a cancer cell.
Today, the relative 5-year survival rate for all cancer diagnoses is around 67 percent, however the figure varies between different diagnoses. Many patients are cured, others are living with a cancer that is considered to be chronic. Research at Karolinska Institutet is also focused on improving therapeutic methods in an attempt to learn more about known genes that can stimulate or inhibit the development of cancer and other such factors. The use of "cancer vaccines" makes it possible to activate and strengthen the body's own defences and thereby develop new methods of treatment.
Radiotherapy and chemotherapy can cure cancer by causing damage to the tumour cells' DNA. However, different cancer cells have different abilities to withstand the treatment. By studying the reasons for this, researchers hope to reduce the risk of therapeutic resistance and to find medicines that counteract it.
One objective is also to be able to act more preventatively. If safer diagnostic methods, such as for the differentiation of aggressiveness in malignant tumours, can be found, as well as more reliable ways of assessing the risk of the cancer spreading and the sensitivity to different therapies, it will enable doctors to provide the best possible treatment as early as possible after diagnosis. The identification and location of specific markers for certain cancer forms will enable doctors to carry out prophylactic (preventative) operations that greatly reduce the risk of cancer.
Karolinska Institutet also conducts research into how to meet the needs of cancer patients and their families, and how to best give relief during the final phase of life.
Haematology is concerned with the blood and its diseases. Blood consists of red and white blood cells, platelets and the plasma which surrounds them, containing various factors. Diseases can develop as the result of deficiencies, for example, anaemia is a lack of red blood cells and haemophilia is caused by a deficiency of coagulation factors.
Cancers of the blood mainly affect different types of white blood cell. Among the most common forms are lymphoma, myeloma and leukaemia. Most of these types of cancer develop in adults and the elderly. Acute leukaemia can also occur in young children where research has contributed to a revolutionary improvement in treatment outcomes over the past few decades.
A biobank is an infrastructural resource for academic and health care-related research. It contains samples of biological material from e. g. tissue or blood, collected for this purpose from patients and others. A biobank enables studies of biological and genetic markers in a large number of samples, to find connections with any disease condition.
The KI Biobank Core Facility is an infrastructural facility for academic and health care-related research, with automated technology designed to ensure sample security and long-term control and distribution of human biological material and data for academic research. Sample collections are also stored at different clinical and preclinical departments at Karolinska Institutet.
Ethical issues and sound scientific principles will be emphasized in the performance of the biobank activities. The concept is that material should be made available on collaboration basis, thus promoting scientific excellence within molecular and genetic research in Sweden. Biobank informatics also involves defining, structuring and standardizing the vast information associated with collected samples.
Biochemistry, pharmacology and metabolism
Cancer research in biochemistry, pharmacology and metabolism is closely related to cell biology. The research includes for example studies of enzymes important for the regulation of growth and protein expression on a biochemical level. New drugs are developed with the intension of blocking growth factors.
The exact three-dimensional structures of biologically essential proteins are determined with x-ray crystallography, which enables further biochemical analyses.
Research on toxic substances effect in the body and its natural defence mechanisms contribute to the development of new medicines.
The effect of potential drugs is also studied, as the tumour cell's response on hormonal substances and other treatments.
This area is focusing on basic mechanisms in causation of tumors and tumor progression, including host responses to tumor development. It includes genetic factors and their protein products, such as oncogenes, cell cycle regulating genes, signal transduction genes, growth factors, apoptosis and cell ageing controls, and suppressor genes and susceptibility genes.
This area also includes studies on genetic cancer susceptibility and familiar cancers, related molecular epidemiology, on the interplay between malignant and normal cells, cell adhesion, angiogenesis, metastasis formation, aspects on tumor regression, and research on the relationship between infections and tumor development, as well as related bioinformatics and biocomplexity.
The application of this knowledge in the development on experimental treatments, such as gene and immunotherapy, and preventive measures is also included in this area of research.
Diagnostics and pathology
To make a diagnosis and describe the disease in question is the basis for a correct treatment. In cancer research many studies are made to refine methods to distinguish variants of for example more or less aggressive cancers. Research is also made to develop methods to follow and follow-up the effects of any given treatment.
In pathology tissue, cells, molecules and genes are studied. Biopsies - tissue samples - from suspected tumours are examined in the microscope. Cytological analyses are made from needle biopsies and cell smears. Tumour cells and cells in pre-cancerous stages can then be found. Molecular and genetic analyses are developed rapidly.
Environment and toxicology
There are many chemical substances in our environment, some of them toxic and/or carcinogenic. Toxic substances occur in the air we breathe and in our food, but also evolve constantly and naturally in the body. The human being has thus – as many other species – developed sophisticated mechanisms for de-codification which protect the body from reactive chemicals.
In biochemical toxicology the biological processes are studied, how they are affected and protected against toxic substances and other foreign matter. Research includes for example studies on how tumours appear and develop.
Epidemiology and biostatistics
Epidemiology is the science of occurrence of diseases in the population. Major steps forward were made with regard to factors that play a role for disease occurrence and disease risk. Causal factors in environment and life style have successfully been studies and in parallel with the development of molecular techniques an increasing number of genetic factors have also been studied in relation to disease occurrence. Epidemiologic methods are used successfully within clinical research to look at treatment results, prognosis, and side effects.
Epidemiological research in Sweden has the advantage of the national registration system of all citizens and high-quality registries of births, deaths and for example cancer diagnoses. At Karolinska Institutet there are several biobanks and also the national Twin Registry. Epidemiological studies are most commonly cohort and case-control studies, or variants thereof. A majority of studies are based on Swedish health registry data, so typically the studies are large, longitudinal and population-based.
Epidemiology of today gives rise to large amounts of data that need statistical analysis. Within biostatistical research statistical methodologies are developed to deal with downstream analysis of the data as well as with the pre-processing of the raw measurements. Statistical tools are explored, developed and used for the design, analysis and interpretation of epidemiological studies.
Cancer has been considered a genetic disease, initially derived from a mutation in an important gene. Emerging knowledge is starting to change this simplified view. The genetic material consists not only of DNA but also of histone proteins. The interpretation of it is not only done through the genetic code of the DNA. In addition there is also an epigenetic code. This code of the epigenome is made up of enzymatic modifications of DNA, as well as the histones, which DNA is associated with. This makes up the histone code.
Since epigenetic changes are observed early in carcinogenesis, it is now increasingly believed that cancer is not only a genetic, but also an epigenetic disease. New basic knowledge within this field is required to understand the origin and treatment of cancer. Ongoing research is addressing questions pertinent to the epigenetic mechanisms of cancer etiology and progression as well as ways of improving therapy by using drugs that alter the epigenome.
It has been shown that these drugs alter cancer cells' interpretation of the genome so that less malignant phenotypes are formed. These changes are being exploited using novel gene therapeutic paradigms and epigenetic "tools" are being tested in combination with traditional chemotherapy in clinical trials to achieve synergistic effects. A close collaboration with the clinic will simplify the transition of basic knowledge to the treatment of patients.
Genetics, genomics and bioinformatics
In cancer research studies of genes and theirs expression are common. Genetics is the biological science of heredity, the molecular basis and function of the genome, how variations appear and what the consequences are. Cancer research in genetics is made e. g. to identify genes that predispose for a certain disease. In most cases there is a combination of genes and environmental factors that imply an increased risk of disease.
Knowledge of genetic factors can be used to prepare general advice and in some cases to design prevention programmes for identified risk groups. Genetics can also be used to distinguish patients with more or less aggressive forms of cancer, as a tool for prognosis and for design of individual cancer treatments.
Genomics is the study of the entire genome, the expression, regulation and interaction of genes. In cancer research genomics is used to study e. g. variations in prevalence and prognosis of different cancer diseases and the underlying causes.
Bioinformatics is a science aiming to analyze the large amount of data that is produced in modern biological research, especially DNA and protein data.
Proteomics and structure biology
Proteomics is the science of protein expression in the human cells. Proteomics can be used in e. g. cancer diagnostics. By analyzing proteins in a tissue sample a healthy patient can be distinguished from a cancer patient or an aggressive, treatment demanding form of cancer can be distinguished from a less aggressive form.
Structural biology comprises the studies of the construction and structure of large macromolecules like proteins and nucleic acids. There is a strong relation between structure and function of proteins and the three-dimensional structure can reveal explanations of e. g. enzymatic activity and the action of co-factors. X-ray crystallography and nuclear magnetic resonance (NMR) are techniques used in structural biology.
Health care research and palliative care
In health care sciences the origin and prerequisites for health and sickness are studied as well as the consequences of disease in biological, psychosocial, public, cultural and economic perspectives. Health care sciences focus on the patients' and their relatives' reactions and experiences of care and treatment.
Health care research in cancer includes studies of the experiences of symptoms, both the actual physical symptoms like pain and difficulty in breathing, and the anxiety that precede or follow. Aspects of nutrition are studied as well as how smell and taste change during cytotoxic treatment. Health care research also deals with how parents and others experience their close relatives' cancer disease, and how they can be supported.
Palliative care in the final stages of life concerns cancer patients as well as other patients with incurable, symptomatic, progressive disease where the expected time of survival is short. The aim of palliative medicine is neither to prolong or to shorten life, but to create quality of life, through active measures and good care, for patients' during their last months' of life.
The palliative care is directed to the patient, but brings support also for their relatives. To be able to meet the needs of the patients and their families, a broad scientific and clinical competence is needed in four dimensions:
- The physical dimension (pain, sickness, fatigue)
- The mental dimension (crisis, anxiety, depression)
- The social dimension (relations, family, housing conditions, losses)
- The existential/spiritual dimension (meaning of life, meaning of suffering, loneliness, guilt, faith, religion)