Poster presentation during Nuclear Receptor Research Network
On Thursday 21st of November, the annual meeting of the Nuclear Receptor research Network (NRRN) took place in Utrecht. PamGene was one of the sponsors of this event. Our dedicated nuclear receptor expert Ren Houtman presented a poster on resistance to endocrine therapy.

Proteomics analysis can help to find combination therapy
The subject of Rene Houtman’s poster are estrogen receptor alpha (ERα)-positive breast cancer patients who display resistance to endocrine therapy. One plausible explanation may be that phosphorylation of ERα leads 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 patient subpopulations show resistance due to alternative (kinase) pathways.

In the current study, ERα activity was characterized in tumour tissue of an endocrine treatment refractory breast cancer patient, using a peptide microarray with coactivator- and -repressor derived motifs (MARCoNI). Phosphatase treatment of a crude tumour 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, the researchers profiled kinase activities in the same tumour sample using kinase substrate arrays on the microarray platform. To identify active kinases, selective inhibitors were added to the sample on chip and the profiles showed a stronger inhibition of a particular kinase. Proteomics analysis of clinical samples at the functional level of multiple drug targets may help to design and select the optimal combination therapy for personalized treatment of breast cancer patients.

This study was performed in co-operation with Dr. Koos van der Hoeven, from Leiden University Medical Center, and under supervision of Dr. Bob Pinedo.