The Ludwig Boltzmann Institute for Cancer Research is focused on basic cancer research to establish molecular insight into the complex disease mechanisms. The resutls are frequently published in high impact journals (see references on PubMed).
Cancer affects everyone in developed nations, either directly or indirectly. While recent developments in palliative care or targeted therapy saw great improvements in cancer therapy in recent years, many patients still succumb to the disease. It is important to note that cancer is not a single disease. There are more than 200 types of cancers, which can be further sub-divided based on complex genetic characteristics. Cancer may affect any part of the body and recent research has established several cancer accelerating processes such as the immune status or chronic tissue damage. Cell damage is often associated with chronic inflammation or infection. In addition, inherited genetic differences influence cancer, which is particularly the reason for childhood cancer development (for example genetic instability and the manifestation of chromosomal breaks or fusions). In adults loss of BRCA1/2 or p53 predisposes to different forms of cancer, other examples are genetic defects in DNA mismatch repair, that drive colon cancer.
Furthermore, due to the heterogeneity of cancer types, each individual disease entity constitutes a complex individual disease and general strategies for therapeutic intervention are difficult to be achieved. Each tumor can be viewed as an organ with complex interactions with the organism. Tumors produce a multitude of signals to evade the immune system, attract blood supply and change the metabolism in their favour. These interactions are essential for tumor growth and might provide attractive avenues to therapeutically tackle the disease. Therefore cancer research relies on animal models mimicking all or many aspects of the heterogeneous genetic disease.
The heterogeneity and complexity of cancer requires individual disease models, which mimic the cellular and genetic events leading to individual cancer types. The LBI-CR focuses on establishing and analysing novel models of cancer by generating appropriate genetic lesions in mice to mimic the human situation. Moreover, a direct comparison to matching human cancer types are performed for a reality check. These models are suitable to investigate the underlying aetiology of cancer development and progression. In addition, they might serve as preclinical models for diagnostic and therapeutic measures to establish clinically relevant proof of concept studies.
Science at the LBI-CR is facilitated through visionary research collaborations with Partner institutions and biotech companies. The Partner-LBI-CR research network analyses phenotypes of transgenic mouse models of cancer and addresses with clinical Partners key questions to battle the disease. The following cancers are currently under investigation: carcinomas of liver, prostate, breast, lung and colon, Ewing's sarcoma, leukemias, lymphomas as well as melanomas.
Moreover, we have established xenograft mouse models in immune-compromised mice for many human tumour entities largely needed for international multi-investigator grant collaborations. Deregulated physiologic processes in liver function cause metabolic problems, fibrosis or chronic inflammation, which are key steps towards liver cancer development studied in detail at the LBI. A common focus in all projects is the core cancer pathway analysis as defined by Prof. B. Vogelstein, a cancer genetics pioneer at the Johns Hopkins University School of Medicine:
"Mutations are just clocks," said Dr. Vogelstein at a recent AACR conference. "Every time a cell divides it mutates at a low rate and those changes are recorded in the cancer genome." The number of driver mutations per cancer cell — those that produce rapid cell division — is another surprisingly concrete number: researchers have identified 117 so far, 70 that are tumor suppressors and 47 that are oncogenes. A driver mutation increases the ratio of cell birth to cell death. "There will be more, but the number is probably not going to be a lot more," Dr. Vogelstein said. All of these genes fit into 12 core signaling pathways. For people who have cancer, the most important cancer genomics outcomes are therapeutic advances. Dr. Vogelstein said that targeted therapeutic agents, such as Gleevec — used in treatment of chronic myeloid leukemia — present great promise.
Our long term goal is to identify methods to improve diagnosis and treatment of cancer. Current basic questions of mouse models aim towards the question which mutations cooperate in the development of different types of cancer. One concept requires again state of the art cancer models to explore the combination of conventional with targeted therapies.