The level of danger posed by tumours depends very much on the tumour cells ability to metastasise i.e. to spread to other body organs where they form secondary tumours. Metastasis makes the treatment of tumours very difficult. In many cases tumours are not diagnosed on the basis of primary tumour symptoms but at a much later stage when secondary tumours have already developed. Metastasis of cancer cells is an important reason for improving the early diagnosis of cancer.
Prof. Dr. Heike Allgayer a surgeon and molecular biologist from Heidelberg is investigating the molecular processes of the formation of tumour metastases. A major objective of her research is to find specific biomarkers that enable the early identification of metastases and to monitor the outcome of therapy. She has already received numerous prizes for her achievements.
Tumour metastases are often resistant to the drug that is used to eliminate the primary tumour. Genome-wide analyses of mutation patterns in the primary tumour and its metastases provide information on the aggressiveness of cancer and may help to find the best available means of further treatment. This has been demonstrated by scientists from Heidelberg in a clinical trial on the molecular evolution of renal cancer.
For the first time, scientists from Heidelberg have characterised cancer cells that initiate metastasis in the blood of breast cancer patients using an in-vivo xenograft mouse model. These cells have the properties of cancer stem cells and are characterised by three surface molecules that can be used as biomarkers for disease progression.
Just a small subpopulation of cancer cells namely metastasis-inducing cancer stem cells MICs is potentially responsible for the formation of distant malignant tumour metastases. The characterisation of MICs and the clarification of mechanisms that lead to their reactivation from a dormant state opens up new strategies for the development of new effective therapies against metastasising tumours.
A single protein can have many variants. This variability is achieved by a process known as splicing which can introduce small modifications into the mRNA transcript of a gene. Prof. Dr. Elmar Stickeler from the University Womens Hospital in Freiburg found that some of these splice variants can also induce cancer. Stickeler and his team are investigating how splicing factors change their target molecules and how this leads to breast cancer. This research is helping to increase our understanding of the molecular basis of cancer as well as potentially also leading to new strategies for the diagnosis and therapy of cancer.
Breast cancer is characterised by broad genetic diversity. Successful treatment is made even more difficult by the fact that, in advanced breast cancer, the properties of metastases often differ significantly from the primary tumour. The Heidelberg CATCH study is now collecting genetic profiles from patients' metastasis tissue samples, which can be used to tailor therapy to individual requirements.
Secretion is a fundamental cellular process. Defects in the secretory pathway have been associated with certain genetic diseases in which the maturation of proteins is disturbed. Non-genetic diseases such as metabolic disorders and cancer have also been linked to a defective secretory pathway. Dr. Hesso Farhan from the University of Konstanz and the Biotechnology Institute Thurgau BITg is investigating possible ways to counteract the development and spread of tumours by interfering with the secretory pathway. Using an innovative method Farhans team of researchers has discovered migration inhibitors which would otherwise have gone undetected.
The German Research Foundation (DFG) is set to establish 17 new collaborative research centres (SFBs) on 1st January 2010. Ten of the new SFBs will focus on life science research projects, and will initially be funded for a period of four years with a total of 78 million euros in funding. One of the SFBs will be established at the University of Freiburg. Six of the 17 new SFBs are SFB/Transregio projects involving researchers from several German research institutions, including two SFBs that are to be coordinated by the University of Heidelberg.
Cathepsins are proteases, i.e. enzymes that break down proteins into smaller fragments. They are also involved in the formation of new blood vessels and wound healing. Another thing that cathepsins do is help tumours spread and form metastases in the body. Prof. Dr. Thomas Reinheckel and his team from the Institute of Molecular Medicine and Cell Research at the University of Freiburg are studying how this happens. Insights into the role of cathepsin L in tumour processes could potentially be exploited for developing cancer therapies that target the progression and metastasis of solid tumours.
The presence of lymph node metastases has a considerable effect on the prognosis and therapy of patients with malignant melanomas. Therefore the histopathological examination of what are known as sentinel lymph nodes the first lymph nodes that metastasising cancer cells reach is of great importance. However the examination method has its technical limitations where very small metastases are concerned. Professor Dr. Anja Ulmer a dermatologist at Tübingen University has now developed a far more sensitive method.
Lung cancer is one of the most common malignant diseases and one of the leading causes of cancer-related deaths worldwide. 90% of all lung cancer cases in men and 80% in women are due to long-term exposure to tobacco smoke. In Germany, around 140 new cases are diagnosed every day, and 50,000 people die of lung cancer every year. PD Dr. Gian Kayser, senior consultant in the Department of Clinical Pathology at Freiburg University Medical Centre, studies the pathogenesis and biology of lung cancer. His aim is to develop new therapies. Kayser and his team have identified the protein MTSS1 as a prognostic factor that can be used to assess the aggressiveness of squamous cell carcinomas before they start to metastasise.
Researchers from Heidelberg have shown that instead of fighting cancer cells, macrophages of the innate immune system promote the growth of metastases in people with metastatic colorectal cancer. They have also shown that a signal inhibitor used to treat HIV infections reactivates macrophages so that they gain the ability to destroy cancer cells. A clinical phase I study has confirmed the antitumoral effects of this drug.
Protein kinases are a major focus of modern cancer research. Since it has become known that these enzymes play a role in the development of tumours, researchers around the world are concentrating on finding drugs to inhibit overactive protein kinases and prevent cancer cells from growing. One of these active substances is currently being tested at the Tumour Biology Centre in Freiburg as part of a worldwide phase III clinical trial.
Colorectal carcinoma is the most frequent type of bowel cancer and the second most common tumour disease in men and women in Germany. A particularly aggressive form occurs when a mutation is present in the proto-oncogene BRAF. As part of the Collaborative Research Centre 850 at the Institute of Molecular Medicine and Cell Research at the University of Freiburg, Dr. Ricarda Herr and Dr. Tilman Brummer are trying to find out how a mutated BRAF gene contributes to the development and growth of colorectal cancer.
Can painful bone metastases be treated in a targeted and quick way? Can metastases that are potentially present in the liver and kidneys be adequately treated at the same time as bone metastases? These are the questions that Professor Dr. med. Frederik Wenz from the University Medical Center Mannheim asked himself before going on to develop an innovative surgical technique. After a long development period, this technique is now recognized as an effective cancer therapy.
Embryonic cells and metastasising cancer cells are able to migrate and intrude into other tissues. Investigations of frog embryos have now provided scientists at the Karlsruhe Institute of Technology with the information that a well-known protein, cadherin-11, triggers cell migration. This glycoprotein is also responsible for the defective behaviour of cells that results in prostate cancer and arthritis.
It is of crucial importance that cells stick tightly together where their function requires them to do so for example in organs such as the heart and the liver to name but two examples. However it is equally crucial that cells start to migrate at some stage during embryonic development in order to form such organs. Prof. Dr. Wolfgang Driever from the Institute of Biology I at the University of Freiburg and his team have elucidated the molecular mechanisms that control the initial movement of cells of the zebrafish Danio rerio embryo. These findings are of major biomedical relevance for example for the understanding of wound healing and the development of cancer.
Claudia Friesen, an oncologist at Ulm University Hospital, has achieved what many scientists dream of: she has made a discovery that has increased existing knowledge, and can be used to help people. People with cancers that are resistant to all conventional therapies who have been given methadone for pain relief in combination with conventional chemo- or radiation therapy, have reported that tumours have shrunk or disappeared completely. Clinical trials that provide evidence for this are not yet available. Professional associations warn of false expectations.
Natural killer cells kill tumour cells by injecting the protein HMGB1, which blocks the production of cellular energy by aerobic respiration. Researchers from Heidelberg have elucidated this previously unknown cancer defence mechanism and are now in the process of developing a new immunotherapy for treating cancer patients.
Apogenix AG, a biopharmaceutical company from Heidelberg that specialises in immuno-oncology, develops protein drugs that target central signalling pathways involved in regulating the growth, migration and apoptosis of malfunctioning cells and thus offer novel treatment options for cancer and other malignant diseases.
Thanks to an innovative treatment procedure that has been in use since 2005, surgeons from Tübingen University Hospital have been able to prolong the survival of patients with peritoneal cancer and give them a higher quality of life. This is done using a technique based on complex surgery followed by immediate intraoperative local chemotherapy on the peritoneum.
While breast cancer survival has clearly improved in recent years, women with triple-negative breast cancer have benefitted very little from progress in cancer medicine. Targeted therapies aimed at inhibiting epigenetic regulators might offer a potential new option for the treatment of breast cancer. Prof. Dr. Roland Schüle and Dr. Jochen Maurer have discovered an epigenetic enzyme called KDM4 and come up with a new cell model that significantly facilitates the development of new cancer drugs.
Liquid biopsy, the analysis of cancer biomarkers and circulating tumour cells in body fluids such as blood, is revolutionising the diagnosis and monitoring of cancer. It has also been possible to expand circulating tumour cells from the blood under laboratory conditions. It is expected that in the future, liquid biopsy will be able to precisely characterise tumour cells at every stage of a cancer.
The German regulatory authority has approved the Clinical Trial Application CTA to begin a Phase I clinical study with RNActive - derived mRNA vaccine CV9103. It will be tested in patients with hormone-refractory metastatic prostate cancer.