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Download: Poster Keystone 2014 Rene Houtman Large

Download: Poster Keystone 2014 Rene Houtman Small
 
 


Abstract: 

Estrogen receptor alpha (ERα) expression is an established biomarker and therapeutic target in breast cancer, however a subpopulation of patients displays resistance towards endocrine treatment. One plausible explanation may be that, in addition to ligand, ERα activity is modulated by post-translational modifications, such as phosphorylation, leading to drug resistance. Combinations of endocrine therapy and kinase inhibiting drugs, e.g. mTOR inhibitor everolimus with the aromatase inhibitor exemestane (BOLERO-2 trial), show success but still leave patient subpopulations resistant due to alternative (kinase) pathways. In the current study, we applied a peptide microarray with coactivator- and -repressor derived motifs (MARCoNI) as a sensor for nuclear receptor activity, i.e. NR conformation and resulting affinity for coregulators, to characterize ERα activity in tumor tissue of an endocrine treatment refractory breast cancer patient. Phosphatase treatment of a crude tumor lysate resulted in modulation of ERα activity, which strongly suggests a role for receptor phosphostatus. To identify the kinase pathway that is responsible for ERα-phosphorylation in this patient, we are currently profiling kinase activities in the same tumor sample using kinase substrate arrays on our microarray platform. Proteomics analysis of clinical samples at the functional/activity level of multiple drug targets, i.e. NRs and kinases, as outlined here, may help to design and select the optimal combination therapy for personalized treatment of breast cancer patients.



About the Author

\"\" Rene Houtman
Senior scientist at PamGene International
Link edIn                                                                                                                         
E-mail: rhoutman@pamgene.com 

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