Pharmacogenomics

To identify specific pharmacological targets in mantle cell lymphoma, this project integrates complementary areas covering all molecular aspects of MCL. Genomic studies (host genetic SNP genetic variability) and RNA micro array analysis of drug resistant tumours will be performed on the IGR research platforms. The preclinical drug discovery strategy will be based on the newly generated cell lines and mouse models of MCL. In the current project the efforts will be devoted to translate the information generated by these molecular pharmacological (pharmacogenomic) studies and animal studies into the clinical practice by performing studies in patient samples of the Clinical MCL Intergroup Working Party. The group will work in an integrated network sharing samples and results that will allow building and testing different predictive models based on the pharmacogenomic profiles. The concomitant generation of preclinical tools for testing specific anticancer drugs against MCL is also integrated in this workpackage. The different partners and activities of this workpackage are:


Objectives:

Chemorefractory primary tumour cells and the emergence of chemoresistance in the course of treatment represent major problems in MCL therapy. Thus, clinical tools are needed to monitor important functional parameters of chemosensitivity in patient cells. However, the molecular basis for this cell resistance is not known: Chemoresistance genes might be stimulated, export pumps might remove cytostatics from the tumour cells or the targets of the therapy might be altered.
Aim of this workpackage is the elucidation of different molecular pathways to determine reliable predictive parameters in the setting of the controlled studies of the European MCL Network. Thus, besides the recently established mouse model to develop preclinical tools for drug discovery, the prognostic relevance of single nucleotide polymorphisms of enzymes involved in the metabolism of various cytostatic drugs will be investigated in the patients of the European MCL Network. Additionally, especially relapsed MCL will be investigated for different molecular alterations.