title: Crossroad between linear and nonlinear transcription concepts in the discovery of next-generation sequencing systems-based anticancer therapies.
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.
authors.affiliation: Centre for Biosystems and Genomic Network Medicine and Research & Innovation Commission of Ioannina University, School of Medicine, Ioannina, Greece; Hellenic Genomic Center and Systems Biology Unit of Biomedical Research Foundation of the Academy of Athens (BRFAA), Athens, Greece. Electronic address: droukos@uoi.gr.
authors.forename: Dimitrios H
authors.initials: DH
authors.lastname: Roukos
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use; D055808:Drug Discovery; D019008:Drug Resistance, Neoplasm; D006801:Humans; D058990:Molecular Targeted Therapy; D009369:Neoplasms / Q000188:drug therapy* / Q000235:genetics; D057285:Precision Medicine; D014158:Transcription, Genetic
chemical_list: D000970:Antineoplastic Agents