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Genome network medicine: innovation to overcome huge challenges in cancer therapy

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The post‐ENCODE era shapes now a new biomedical research direction for understanding transcriptional and signaling networks driving gene expression and core cellular processes such as cell fate, survival, and apoptosis. Over the past half century, the Francis Crick ‘central dogma’ of single n gene/protein‐phenotype (trait/disease) has defined biology, human physiology, disease, diagnostics, and drugs discovery. However, the ENCODE project and several other genomic studies using high‐throughput sequencing technologies, computational strategies, and imaging techniques to visualize regulatory networks, provide evidence that transcriptional process and gene expression are regulated by highly complex dynamic molecular and signaling networks. This Focus article describes the linear experimentation‐based limitations of diagnostics and therapeutics to cure advanced cancer and the need to move on from reductionist to network‐based approaches. With evident a wide genomic heterogeneity, the power and challenges of next‐generation sequencing (NGS) technologies to identify a patient's personal mutational landscape for tailoring the best target drugs in the individual patient are discussed. However, the available drugs are not capable of targeting aberrant signaling networks and research on functional transcriptional heterogeneity and functional genome organization is poorly understood. Therefore, the future clinical genome network medicine aiming at overcoming multiple problems in the new fields of regulatory DNA mapping, noncoding RNA, enhancer RNAs, and dynamic complexity of transcriptional circuitry are also discussed expecting in new innovation technology and strong appreciation of clinical data and evidence‐based medicine. The problematic and potential solutions in the discovery of next‐generation, molecular, and signaling circuitry‐based biomarkers and drugs are explored. WIREs Syst Biol Med 2014, 6:201–208. doi: 10.1002/wsbm.1254

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Biological Mechanisms > Regulatory Biology
Laboratory Methods and Technologies > Genetic/Genomic Methods
Translational, Genomic, and Systems Medicine > Therapeutic Methods

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In the Spotlight

Merryn Tawhai

Merryn Tawhai

Dr. Tawhai is PI for lung modeling activities at the Auckland Bioengineering Institute and adjunct Associate Professor of Biomedical Engineering at the University of Iowa. Her research centers on developing multi-scale and multi-physics computational models of structure and function in the lung. A theme that runs through all of her work is the relationship between regional changes in lung structure or function and standard integrated measurements of the lung that are made at the mouth.

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