RESEARCH

 

 

Functional validation in preclinical model systems

State-of-the-art technologies such as RNAinterference and mouse tumour models will be used in these investigations to deepen the understanding of the biological mechanisms and pathways involved in chemoresistance in melanoma and lung cancer. The preclinical model systems already described will be used.

  1. We will perform transient siRNA inhibition of 20 to 40 candidate genes in lung cancer and melanoma cell lines and/or stem cells.
  2. Transfection of 10 to 20 candidate genes will be performed in a selection of cell lines and/or stem cells. We will then assess effects on drug resistance, on phenotype markers and assess changes in apoptosis regulated chemoresistance to drugs.
  3. These results will be used to select the top 5-10 candidate genes.
  4. A second round of genomic investigations with pangenomic microarrays will then be performed in a panel of 5 cell lines using the top 5-10 siRNAs, in drug treated and untreated cells.
  5. These results will then be subjected to a last round of integrative bioinformatics analysis which will lead to
  6. A final report on a limited number of clinically and functionally validated genes and a description of underlying mechanisms of resistance.
Page updated by Chemores May 23, 2007
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