Molecular classification of solid tumours: towards pathway-driven therapeutics.
The last decade has witnessed unprecedented developments in the genetic and epigenetic analyses of solid tumours. Transcriptional and DNA copy-number studies have improved our understanding and classification of solid tumours and highlighted the patterns of genomic aberrations associated with outcome. The identification of altered transcriptional and translational silencing by microRNAs and epigenetic modification by methylation in tumours has showed a layer of additional intricacy to the regulation of gene expression in different tumour types. The advent of massive parallel sequencing has allowed whole cancer genomes to be sequenced with extraordinary speed and accuracy providing insight into the bewildering complexity of gene mutations present in solid tumours. Functional genomic studies using RNA interference-screening tools promises to improve the classification of solid tumours by probing the relevance of each gene to tumour phenotype. In this review, we discuss how these studies have contributed to solid tumour classification and why such studies are central to the future of oncology. We suggest that these developments are gradually leading to a change in emphasis of early clinical trials to a therapeutic model guided by the molecular classification of tumours. The investigation of drug efficacy later in development is beginning to rely on patient selection defined by predictive molecular criteria that complement solid tumour classification based on anatomic site.
Swanton
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Translational Cancer Therapeutics Laboratory, Cancer Research UK London Research Institute, London, UK.
Caldas
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D043171:Chromosomal Instability / Q000502:physiology; D016503:Drug Delivery Systems / Q000379:methods / Q000639:trends*; D018628:Gene Dosage; D020869:Gene Expression Profiling; D006801:Humans; D035683:MicroRNAs / Q000235:genetics / Q000502:physiology; D008954:Models, Biological; D009369:Neoplasms / Q000145:classification* / Q000175:diagnosis / Q000235:genetics* / Q000628:therapy*; D011379:Prognosis; D015398:Signal Transduction / Q000235:genetics*
D035683:MicroRNAs