High-throughput molecular analysis in lung cancer: insights into biology and potential clinical applications.
During the last decade, high-throughput technologies including genomic, epigenomic, transcriptomic and proteomic have been applied to further our understanding of the molecular pathogenesis of this heterogeneous disease, and to develop strategies that aim to improve the management of patients with lung cancer. Ultimately, these approaches should lead to sensitive, specific and noninvasive methods for early diagnosis, and facilitate the prediction of response to therapy and outcome, as well as the identification of potential novel therapeutic targets. Genomic studies were the first to move this field forward by providing novel insights into the molecular biology of lung cancer and by generating candidate biomarkers of disease progression. Lung carcinogenesis is driven by genetic and epigenetic alterations that cause aberrant gene function; however, the challenge remains to pinpoint the key regulatory control mechanisms and to distinguish driver from passenger alterations that may have a small but additive effect on cancer development. Epigenetic regulation by DNA methylation and histone modifications modulate chromatin structure and, in turn, either activate or silence gene expression. Proteomic approaches critically complement these molecular studies, as the phenotype of a cancer cell is determined by proteins and cannot be predicted by genomics or transcriptomics alone. The present article focuses on the technological platforms available and some proposed clinical applications. We illustrate herein how the "-omics" have revolutionised our approach to lung cancer biology and hold promise for personalised management of lung cancer.
Ocak
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Division of Allergy, Pulmonary and Critical Care Medicine, Vanderbilt-Ingram Cancer Center, Nashville, TN 37232-6838, USA.
Sos
M L
ML
Thomas
R K
RK
Massion
P P
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D015415:Biomarkers / Q000378:metabolism; D002843:Chromatin / Q000737:chemistry; D019175:DNA Methylation; D018450:Disease Progression; D044127:Epigenesis, Genetic; D020869:Gene Expression Profiling; D023281:Genomics; D006657:Histones / Q000737:chemistry; D006801:Humans; D008175:Lung Neoplasms / Q000175:diagnosis* / Q000235:genetics* / Q000378:metabolism / Q000628:therapy; D009369:Neoplasms / Q000378:metabolism; D009693:Nucleic Acid Hybridization; D040081:Protein Array Analysis; D040901:Proteomics / Q000379:methods; D014158:Transcription, Genetic
D015415:Biomarkers; D002843:Chromatin; D006657:Histones