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  1. Article ; Online: Spatiotemporal diversification of intrapatient genomic clones and early drug development concepts realize the roadmap of precision cancer medicine.

    Roukos, Dimitrios H

    Drug discovery today

    2017  Volume 22, Issue 8, Page(s) 1148–1164

    Abstract: The unmet clinical needs of high relapse and cancer-related death rates are reflected by the poor understanding of the genome-wide mutational landscape and molecular mechanisms orchestrating therapeutic resistance. Emerging potential solutions to this ... ...

    Abstract The unmet clinical needs of high relapse and cancer-related death rates are reflected by the poor understanding of the genome-wide mutational landscape and molecular mechanisms orchestrating therapeutic resistance. Emerging potential solutions to this challenge include the exploration of cancer genome dynamic evolution in time and space. Breakthrough next-generation sequencing (NGS) applications including multiregional NGS for intratumor heterogeneity identification, repeated cell-free DNA/circulating tumor DNA-NGS for detecting circulating genomic subclones and their comparison to reveal intrapatient heterogeneity (IPH) could identify the dynamic emergence of resistant subclones in the neoadjuvant, adjuvant and metastatic setting. Based on genome-phenotype map, and potential promising findings, rigorous evaluation of IPH spatiotemporal evolution and early drug development concepts in innovative clinical trials could dramatically speed up the translational process to achieve clinical precision oncology.
    Language English
    Publishing date 2017-08
    Publishing country England
    Document type Journal Article ; Review
    ZDB-ID 1324988-5
    ISSN 1878-5832 ; 1359-6446
    ISSN (online) 1878-5832
    ISSN 1359-6446
    DOI 10.1016/j.drudis.2017.03.014
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    Zs.A 4725: Show issues Location:
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  2. Article ; Online: Crossroad between linear and nonlinear transcription concepts in the discovery of next-generation sequencing systems-based anticancer therapies.

    Roukos, Dimitrios H

    Drug discovery today

    2016  Volume 21, Issue 4, Page(s) 663–673

    Abstract: The unprecedented potential of standard and new next-generation sequencing applications and methods to explore cancer genome evolution and tumor heterogeneity as well as transcription networks in time and space shapes the development of next-generation ... ...

    Abstract The unprecedented potential of standard and new next-generation sequencing applications and methods to explore cancer genome evolution and tumor heterogeneity as well as transcription networks in time and space shapes the development of next-generation therapeutics. However, biomedical and pharmaceutical research for overcoming heterogeneity-based therapeutic resistance is at an important crossroads. Focus on linear transcription-based drug development targeting dynamics of simple intrapatient structured genome diversity represents a realistic medium-term goal. By contrast, the discovery of nonlinear transcription drugs for targeting structural and functional genome and transcriptome heterogeneity represents a long-term rational strategy. This review compares effectiveness, challenges and expectations between linear and nonlinear drugs targeting simple intrapatient variation and aberrant transcriptional biocircuits, respectively.
    MeSH term(s) Antineoplastic Agents/therapeutic use ; Drug Discovery ; Drug Resistance, Neoplasm ; Humans ; Molecular Targeted Therapy ; Neoplasms/drug therapy ; Neoplasms/genetics ; Precision Medicine ; Transcription, Genetic
    Chemical Substances Antineoplastic Agents
    Language English
    Publishing date 2016-04
    Publishing country England
    Document type Journal Article ; Review
    ZDB-ID 1324988-5
    ISSN 1878-5832 ; 1359-6446
    ISSN (online) 1878-5832
    ISSN 1359-6446
    DOI 10.1016/j.drudis.2016.02.008
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Longitudinal ctDNA profiling in precision oncology and immunο-oncology.

    Filis, Panagiotis / Kyrochristos, Ioannis / Korakaki, Efterpi / Baltagiannis, Evangelos G / Thanos, Dimitris / Roukos, Dimitrios H

    Drug discovery today

    2023  Volume 28, Issue 4, Page(s) 103540

    Abstract: Serial analysis of circulating tumor DNA (ctDNA) over the disease course is emerging as a prognostic, predictive and patient-monitoring biomarker. In the metastatic setting, several multigene ctDNA assays have been approved or recommended by regulatory ... ...

    Abstract Serial analysis of circulating tumor DNA (ctDNA) over the disease course is emerging as a prognostic, predictive and patient-monitoring biomarker. In the metastatic setting, several multigene ctDNA assays have been approved or recommended by regulatory organizations for personalized targeted therapy, especially for lung cancer. By contrast, in nonmetastatic disease, detection of ctDNA resulting from minimal residual disease (MRD) following multimodal treatment with curative intent presents major technical challenges. Several studies using tumor genotyping-informed serial ctDNA profiling have provided promising findings on the sensitivity and specificity of ctDNA in predicting the risk of recurrence. We discuss progress, limitations and future perspectives relating to the use of ctDNA as a biomarker to guide targeted therapy in metastatic disease, as well as the use of ctDNA MRD detection to guide adjuvant treatment in the nonmetastatic setting.
    MeSH term(s) Humans ; Biomarkers, Tumor/genetics ; Circulating Tumor DNA/genetics ; Lung Neoplasms/drug therapy ; Lung Neoplasms/genetics ; Neoplasm Recurrence, Local ; Precision Medicine ; Prognosis ; Medical Oncology
    Chemical Substances Biomarkers, Tumor ; Circulating Tumor DNA
    Language English
    Publishing date 2023-02-21
    Publishing country England
    Document type Journal Article ; Review
    ZDB-ID 1324988-5
    ISSN 1878-5832 ; 1359-6446
    ISSN (online) 1878-5832
    ISSN 1359-6446
    DOI 10.1016/j.drudis.2023.103540
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Comprehensive intra-individual genomic and transcriptional heterogeneity: Evidence-based Colorectal Cancer Precision Medicine.

    Kyrochristos, Ioannis D / Roukos, Dimitrios H

    Cancer treatment reviews

    2019  Volume 80, Page(s) 101894

    Abstract: Despite advances in translating conventional research into multi-modal treatment for colorectal cancer (CRC), therapeutic resistance and relapse remain unresolved in advanced resectable and, particularly, non-resectable disease. Genome and transcriptome ... ...

    Abstract Despite advances in translating conventional research into multi-modal treatment for colorectal cancer (CRC), therapeutic resistance and relapse remain unresolved in advanced resectable and, particularly, non-resectable disease. Genome and transcriptome sequencing and editing technologies, coupled with interaction mapping and machine learning, are transforming biomedical research, representing the most rational hope to overcome unmet research and clinical challenges. Rapid progress in both bulk and single-cell next-generation sequencing (NGS) analyses in the identification of primary and metastatic intratumor genomic and transcriptional heterogeneity (ITH) and the detection of circulating cell-free DNA (cfDNA) alterations is providing critical insight into the origins and spatiotemporal evolution of genomic clones responsible for early and late therapeutic resistance and relapse. Moreover, DNA and RNA editing pave new avenues towards the discovery of novel drug targets. Breakthrough combinations of sequencing and editing systems with technologies exploring dynamic interaction networks within pioneering studies could delineate how coding and non-coding mutations perturb regulatory networks and gene expression. This review discusses latest data on genomic and transcriptomic landscapes in time and space, as well as early-phase clinical trials on targeted drug combinations, highlighting the transition from research to clinical Colorectal Cancer Precision Medicine, through non-invasive screening, individualized drug response prediction and development of multiple novel drugs. Future studies exploring the potential to target key transcriptional drivers and regulators will contribute to the next-generation pharmaceutical controllability of multi-layered aberrant transcriptional biocircuits.
    MeSH term(s) Animals ; Colorectal Neoplasms/genetics ; DNA, Neoplasm/genetics ; Genomics/methods ; Humans ; Precision Medicine ; RNA, Neoplasm/genetics ; Transcription, Genetic
    Chemical Substances DNA, Neoplasm ; RNA, Neoplasm
    Language English
    Publishing date 2019-09-03
    Publishing country Netherlands
    Document type Journal Article ; Review
    ZDB-ID 125102-8
    ISSN 1532-1967 ; 0305-7372
    ISSN (online) 1532-1967
    ISSN 0305-7372
    DOI 10.1016/j.ctrv.2019.101894
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    Zs.MO 611: Show issues

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  5. Article ; Online: Precision in cancer pharmacogenomics.

    Kyrochristos, Ioannis D / Baltagiannis, Evangelos G / Mitsis, Michail / Roukos, Dimitrios H

    Pharmacogenomics

    2020  Volume 21, Issue 5, Page(s) 311–316

    MeSH term(s) Humans ; Pharmacogenetics ; Precision Medicine ; Neoplasms/drug therapy ; Neoplasms/genetics
    Language English
    Publishing date 2020-04-03
    Publishing country England
    Document type Editorial
    ZDB-ID 2019513-8
    ISSN 1744-8042 ; 1462-2416
    ISSN (online) 1744-8042
    ISSN 1462-2416
    DOI 10.2217/pgs-2020-0011
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    Zs.A 5247: Show issues Location:
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  6. Article ; Online: Genome network medicine: innovation to overcome huge challenges in cancer therapy.

    Roukos, Dimitrios H

    Wiley interdisciplinary reviews. Systems biology and medicine

    2014  Volume 6, Issue 2, Page(s) 201–208

    Abstract: 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 ... ...

    Abstract 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.
    MeSH term(s) Antineoplastic Agents/pharmacology ; Antineoplastic Agents/therapeutic use ; Gene Expression Regulation, Neoplastic ; Gene Regulatory Networks ; Genetic Heterogeneity ; Genome, Human ; Genome-Wide Association Study ; High-Throughput Nucleotide Sequencing ; Humans ; Neoplasms/drug therapy ; Neoplasms/genetics ; Neoplasms/metabolism ; Sequence Analysis, DNA ; Signal Transduction/drug effects
    Chemical Substances Antineoplastic Agents
    Language English
    Publishing date 2014-03
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2503323-2
    ISSN 1939-005X ; 1939-5094
    ISSN (online) 1939-005X
    ISSN 1939-5094
    DOI 10.1002/wsbm.1254
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: Cancer heterogeneity and signaling network-based drug target.

    Roukos, Dimitrios H

    Pharmacogenomics

    2013  Volume 14, Issue 11, Page(s) 1243–1246

    MeSH term(s) DNA Mutational Analysis ; Genetic Heterogeneity ; High-Throughput Nucleotide Sequencing ; Humans ; Molecular Targeted Therapy ; Neoplasms/drug therapy ; Neoplasms/genetics ; Neoplasms/pathology ; Precision Medicine ; Signal Transduction/genetics
    Language English
    Publishing date 2013-08
    Publishing country England
    Document type Editorial
    ZDB-ID 2019513-8
    ISSN 1744-8042 ; 1462-2416
    ISSN (online) 1744-8042
    ISSN 1462-2416
    DOI 10.2217/pgs.13.113
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    Zs.A 5247: Show issues Location:
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  8. Article ; Online: Genome network medicine: new diagnostics and predictive tools.

    Roukos, Dimitrios H

    Expert review of molecular diagnostics

    2013  Volume 13, Issue 7, Page(s) 643–646

    MeSH term(s) Computational Biology ; Gene Expression Regulation ; Gene Regulatory Networks ; Genome, Human ; High-Throughput Nucleotide Sequencing ; Humans ; Molecular Diagnostic Techniques ; Precision Medicine ; Protein Interaction Maps
    Language English
    Publishing date 2013-09
    Publishing country England
    Document type Editorial
    ZDB-ID 2112530-2
    ISSN 1744-8352 ; 1473-7159
    ISSN (online) 1744-8352
    ISSN 1473-7159
    DOI 10.1586/14737159.2013.820540
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  9. Article ; Online: Integrated clinical genomics: new horizon for diagnostic and biomarker discoveries in cancer.

    Roukos, Dimitrios H

    Expert review of molecular diagnostics

    2013  Volume 13, Issue 1, Page(s) 1–4

    MeSH term(s) Biomarkers, Tumor/genetics ; Breast Neoplasms/diagnosis ; Breast Neoplasms/genetics ; Chromosome Mapping ; Colorectal Neoplasms/diagnosis ; Colorectal Neoplasms/genetics ; Female ; Genomics ; High-Throughput Screening Assays ; Humans ; Molecular Diagnostic Techniques ; Precision Medicine
    Chemical Substances Biomarkers, Tumor
    Language English
    Publishing date 2013-01
    Publishing country England
    Document type Editorial
    ZDB-ID 2112530-2
    ISSN 1744-8352 ; 1473-7159
    ISSN (online) 1744-8352
    ISSN 1473-7159
    DOI 10.1586/erm.12.132
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  10. Article ; Online: Differential signaling transduction networks for clinical robustness.

    Roukos, Dimitrios H

    Expert review of proteomics

    2012  Volume 9, Issue 2, Page(s) 111–114

    MeSH term(s) Chromosome Mapping ; Gene Expression Regulation ; Gene Regulatory Networks ; Humans ; Protein Interaction Mapping ; Signal Transduction
    Language English
    Publishing date 2012-04
    Publishing country England
    Document type Editorial
    ZDB-ID 2299100-1
    ISSN 1744-8387 ; 1478-9450
    ISSN (online) 1744-8387
    ISSN 1478-9450
    DOI 10.1586/epr.12.14
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