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Integrated Genomics of Treatment Resistance

The Laboratory of "Integrated genomics of treatment resistance” studies breast and ovarian cancer to identify genotypes, gene expression profiles and pathways contributing to cancer risk, tumor aggressiveness and treatment resistance.
The main goal of the research group is to identify drug response biomarkers and drugable targets in order to improve treatment response.


The current research focuses on:
A) Characterization of cfDNA, miRNA, mRNA and protein expression profiles, SNPs and mutations, pathways, and histone modifications in predicting treatment outcome.

B) In silico and in vitro integrated analysis of treatment response profiles.

C) Ovarian cancer model studies. Primary and therapy resistant material, with flollow-up,  retro- en prospective collected material (Ascites, Tumors, Sera-plasma collected during therapy). The objectives are to characterize the genotype and phenotype of tumors in cancer cell lines  and integrate these to obtain expression profiles and pathways associated with drug responses. To assess whether biomarkers are putative drugable targets, functional studies in 39 well characterized ovarian cancer cell lines (Beaufort et al, Plos one 2014) are performed. 

The integration of these results will aid in the individualization of the treatment of patients with respect to choice of drugs and possibly dose and duration. This may give a better therapeutic efect and less adverse reactions in the individual patient. 

The aim is to conquer treatment resistance through research and education.

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Publications

Key publications:
Jansen, MPHM, Foekens JA, van Staveren IL, Dirkzwager-Kiel MM, Ritstier K, Look MP, Meijer-van Gelder ME,  Sieuwerts AM, Portengen H, Dorssers LCJ, Klijn JGM,  Berns EMJJ. Molecular classification of tamoxifen resistant breast carcinomas by gene-expression profiling. Journal of Clinical Oncology, 23, 732-740 (2005). PubMed

Wang Y, Klijn JGM, Zhang Y, Sieuwerts AM, Look MP, Yang F, Talantov D, Timmermans M, Meijer-van Gelder ME, Yu J, Jatkoe T, Berns EMJJ, Atkins D, Foekens JA. Gene expression profiles to predict distant metastasis of early breast cancer. Lancet, 365, 671-679, 2005. PubMed
 
Helleman J, Jansen MPHM, Span PN, van Staveren IL, Massuger LFAG, Meijer-van Gelder ME, Sweep FCGJ, Ewing PC, van der Burg MEL, Stoter G, Nooter K, Berns EMJJ. Molecular profiling of platinum resistant ovarian cancer. Int J Cancer, 118, 1963-1971 (2006). PubMed

2 recent publications: 
Berns EMJJ and Bowtell DD. The changing view of high grade serous ovarian cancer. Cancer Res, 2012, 72, 2701-2704. PubMed
 
Jansen MPHM, Knijnenburg Th, Reijm EA, Simon I, Kerkhoven R, Velds A, van Laere S, Dirix L, Alexi X, Foekens JA, Wessels L, Linn S, Zwart WT Berns EM. Hallmarks of aromatase inhibitor drug resistance revealed by epigenetic profiling in breast cancer. Cancer Res 2013, 15: 6632-41. PubMed