In the Research Line Molecular Oncology the genotypic and phenotypic characterization of different types of cancer is used to unravel basic molecular processes that play an important role during carcinogenesis and progression of cancer. The results of these molecular approaches are extended to investigations in the clinic, which results in the recognition of new and improved diagnostic and prognostic indicators. Furthermore, these insights can give a strong impetus to new therapeutic and preventive strategies.
The projects in this research line include:
The studies on genetic changes that play a role in the initiation of the carcinogenic process
Amongst these are the studies on the re-expression of embryonic genes during oncogenesis, the role of HPV infection and integration, the role of UV-induced mutagenesis, the role of DNA-methylation and studies on initial genetic insults in the stem cells of several tissues resulting in oncogenesis.
The studies on genetic instability resulting in the progression of cancer
Amongst these are the studies on specific chromosome aberrations that indicate the status of the disease, for example in cancer of the bladder, neuroendocrine tissues, colon, cervix, ovary, breast and endometrium, skin, head and neck epithelia and brain. The recognition of these genetic changes has not only diagnostic potential for tumor staging, tumor identification and prognostication, but also provided essential insights into the role of the genomic aberrations in the progression of malignancy.
The studies on DNA repair systems that counteract damage produced by endogenous and exogenous agents
Lesions produced by UV light and the chemotherapeutic drug cisplatin, are physically removed by the NER complex. However, despite this activity as well as the presence of cell-cycle checkpoints, repair often does not occur before replication of the DNA containing the lesion is attempted. These lesions may subsequently block the progression of DNA polymerases, and cells have developed mechanisms to bypass such lesions. The genes in this post-replication repair pathway encode proteins involved in ubiquitination.
The studies on dietary factors and specific gene mutations in colon carcinogenesis
These studies correlate the susceptibility for colon cancer to dietary factors and mutations in specific genes, such as APC and K-ras. Also the role of dietary factors on gene methylation during colon carcinogenes is studied in detail.
The studies into cancer phenotypes, in which much attention is focused on the relationship between the above mentioned genomic changes on the one hand, and the proliferative activity and apoptotic potential on the other. In particular the process of apoptosis is studied in detail at the molecular level, which has not only resulted in several new assays, but also provided insight into the role of the apoptotic signaling pathways and of the cytoskeleton in determining the apoptotic potential of cancer cells.
The studies into the identification of cancer related antigens, such as specific splice variants of cell surface proteins, which can be used as targets for (DNA) vaccination protocols. A European consortium is being funded by the EU to identify and apply such targets for lung cancer.
top