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Laboratory of Molecular and Medical Oncology

Research Group

Main organisation:Research Council
Lifecycle:20 Oct 2010 →  Today
Organisation profile:

1. Clinical studies to assess the tolerability and efficacy of novel systemic treatments of cancer (phase I, II, III); sponsored and academic studies. Clinical studies also encompass studies that aim at increasing the quality of cancer care with studies in end of life and in geriatric oncology 2. Translational studies in various cancer types that specifically aim at correlating biomarkers with the clinical efficacy of novel cancer treatments. A major focus is on genomic biomarker research and the application in the clinic. This is motivated by the growing scientific and health economic need for the optimal application of novel molecular targeted therapies (monoclonal antibodies and small molecules). The purpose is to come to scientifically based patient enrichment that maximises the therapeutic ratio. The strong existing evidence that only genomically activated cancer genes constitute hard therapeutic targets is the basis for translational studies run within the department. A strong genomic laboratory tightly connected to the clinical activity creates a context in which the UZ Brussel can take the initiative and lead in innovative translational studies. The laboratory has gained a specific expertise in the extraction of genetic material from minute tumor biopsies and cytologies that enables the mutation analysis of cancer genes. This effort is also in collaboration with the pathology department of the UZ Brussel (Peter in 't Veld PhD, Caroline Geers MD, Claire Bourgain MD, PhD, Anne Hoorens MD, PhD) that performs the necessary pathological, immunhistochemical and FISH examinations, which allows also the study of gene copy number and rearrangements. Translational studies have been performed or are ongoing in following tumor types: lung cancer, brain tumours, melanoma, sarcoma and oesophageal cancer. More recently we have also initiated the measurement of circulating tumor and endothelial cells, as an explorative biomarker in some of these translational studies and also exploring them as a source for tumor DNA, which might be useful especially when tumour biopsies are not available for genomic analysis. This work is in collaboration with Isabelle Vande Broek MD, PhD and Ivan Van Riet, PhD. 3. Preclinical assessment of targeted anticancer agents with a focus on the HER pathway. BaF/3 cells transfected with wild-type and mutant HER receptors and lung cancer cell lines are used to comparatively test small molecules as single agents and in combinations. A recent research topic, in collaboration with Peter Kronenberger, is an attempt at inhibiting HER receptors by designing siRNA's that specifically interact with mutant receptors that are resistant to tyrosine kinase inhibitors. The investigational plan is to investigate whether these can be linked to anti-EGFR nanobodies and thus be explored in in vivo models. The rationale behind this research is dual: receptors can become resistant to small molecules (secondary resistance mutations). But also it appears from preclinical evidence that even the most efficient shutting down of the kinase activity of these receptors with small molecules does not annul completely the role of the receptor in the maintenance of the malignant phenotype and there is thus room for investigation of alternative strategies. 4. Genetic cancer with an emphasis on breast/ovarian cancer in relationship to the Familial Cancer Clinic of the Oncologisch centrum. a. Clinical research involving methodology of cancer genetic counseling b. Research in breast cancer predisposition genes c. Participation in development of specific targeted agents in genetic cancer The laboratory performs and supervises the routine analysis of the BRCA1&2 genes (with also technical cooperation from the genetics department, collaboration with Willy Lissens, PhD) in the context of genetic counselling. A large proportion of families with a strong family history of breast and or ovarian cancer do not have mutations in BRCA1&2 genes and in these families other genes, not previously associated with genetic breast cancer have been investigated. The underlying hypothesis was that in such families the defect could be in a gene that produces a protein which is on the pathway of BRCA1&2. This strategy has lead so far to the identification of 2 novel breast cancer predisposition genes: BARD1 and NPM1. The importance of the diagnosis of genetic cancer has increased even more since the discovery of treatments that have a selective activity and cancers that originate in such patients (PARP inhibitor). The availability of an efficient testing lab has allowed our participation in early clinical studies with a PARP1 inhibitor. 5. Therapeutic cancer vaccination In collaboration with FYSP, clinical translational studies are organized to investigate the therapeutic potential of antigen transduced autologous dendritic cells and other immunotherapeutic modalities.