TY - JOUR
T1 - Tamoxifen integromics and personalized medicine
T2 - Dynamic modular transformations underpinning response to tamoxifen in breast cancer treatment
AU - Dimitrakopoulou, Konstantina
AU - Dimitrakopoulos, Georgios N.
AU - Sgarbas, Kyriakos N.
AU - Bezerianos, Anastasios
PY - 2014/1/1
Y1 - 2014/1/1
N2 - Recent advances in pharmacogenomics technologies allow bold steps to be taken towards personalized medicine, more accurate health planning, and personalized drug development. In this framework, systems pharmacology network-based approaches offer an appealing way for integrating multi-omics data and set the basis for defining systems-level drug response biomarkers. On the road to individualized tamoxifen treatment in estrogen receptor-positive breast cancer patients, we examine the dynamics of the attendant pharmacological response mechanisms. By means of an "integromics" network approach, we assessed the tamoxifen effect through the way the high-order organization of interactome (i.e., the modules) is perturbed. To accomplish that, first we integrated the time series transcriptome data with the human protein interaction data, and second, an efficient module-detecting algorithm was applied onto the composite graphs. Our findings show that tamoxifen induces severe modular transformations on specific areas of the interactome. Our modular biomarkers in response to tamoxifen attest to the immunomodulatory role of tamoxifen, and further reveal that it deregulates cell cycle and apoptosis pathways, while coordinating the proteasome and basal transcription factors. To the best of our knowledge, this is the first report that informs the fields of personalized medicine and clinical pharmacology about the actual dynamic interactome response to tamoxifen administration.
AB - Recent advances in pharmacogenomics technologies allow bold steps to be taken towards personalized medicine, more accurate health planning, and personalized drug development. In this framework, systems pharmacology network-based approaches offer an appealing way for integrating multi-omics data and set the basis for defining systems-level drug response biomarkers. On the road to individualized tamoxifen treatment in estrogen receptor-positive breast cancer patients, we examine the dynamics of the attendant pharmacological response mechanisms. By means of an "integromics" network approach, we assessed the tamoxifen effect through the way the high-order organization of interactome (i.e., the modules) is perturbed. To accomplish that, first we integrated the time series transcriptome data with the human protein interaction data, and second, an efficient module-detecting algorithm was applied onto the composite graphs. Our findings show that tamoxifen induces severe modular transformations on specific areas of the interactome. Our modular biomarkers in response to tamoxifen attest to the immunomodulatory role of tamoxifen, and further reveal that it deregulates cell cycle and apoptosis pathways, while coordinating the proteasome and basal transcription factors. To the best of our knowledge, this is the first report that informs the fields of personalized medicine and clinical pharmacology about the actual dynamic interactome response to tamoxifen administration.
UR - http://www.scopus.com/inward/record.url?scp=84893041759&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84893041759&partnerID=8YFLogxK
U2 - 10.1089/omi.2013.0055
DO - 10.1089/omi.2013.0055
M3 - Article
C2 - 24299457
AN - SCOPUS:84893041759
SN - 1536-2310
VL - 18
SP - 15
EP - 33
JO - OMICS A Journal of Integrative Biology
JF - OMICS A Journal of Integrative Biology
IS - 1
ER -