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Cancers 2018, 10(8), 248; https://doi.org/10.3390/cancers10080248

Lung Cancers: Molecular Characterization, Clonal Heterogeneity and Evolution, and Cancer Stem Cells

Department of Hematology, Oncology and Molecular Medicine, Istituto Superiore di Sanità, 00161 Rome, Italy
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Received: 5 June 2018 / Revised: 19 July 2018 / Accepted: 20 July 2018 / Published: 27 July 2018
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Abstract

Lung cancer causes the largest number of cancer-related deaths in the world. Most (85%) of lung cancers are classified as non-small-cell lung cancer (NSCLC) and small-cell lung cancer (15%) (SCLC). The 5-year survival rate for NSCLC patients remains very low (about 16% at 5 years). The two predominant NSCLC histological phenotypes are adenocarcinoma (ADC) and squamous cell carcinoma (LSQCC). ADCs display several recurrent genetic alterations, including: KRAS, BRAF and EGFR mutations; recurrent mutations and amplifications of several oncogenes, including ERBB2, MET, FGFR1 and FGFR2; fusion oncogenes involving ALK, ROS1, Neuregulin1 (NRG1) and RET. In LSQCC recurrent mutations of TP53, FGFR1, FGFR2, FGFR3, DDR2 and genes of the PI3K pathway have been detected, quantitative gene abnormalities of PTEN and CDKN2A. Developments in the characterization of lung cancer molecular abnormalities provided a strong rationale for new therapeutic options and for understanding the mechanisms of drug resistance. However, the complexity of lung cancer genomes is particularly high, as shown by deep-sequencing studies supporting the heterogeneity of lung tumors at cellular level, with sub-clones exhibiting different combinations of mutations. Molecular studies performed on lung tumors during treatment have shown the phenomenon of clonal evolution, thus supporting the occurrence of a temporal tumor heterogeneity. View Full-Text
Keywords: non-small cell lung cancer; small cell lung cancer; cancer stem cells; genomic profiling; membrane cell markers; tumor xenotransplantation assay non-small cell lung cancer; small cell lung cancer; cancer stem cells; genomic profiling; membrane cell markers; tumor xenotransplantation assay
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Testa, U.; Castelli, G.; Pelosi, E. Lung Cancers: Molecular Characterization, Clonal Heterogeneity and Evolution, and Cancer Stem Cells. Cancers 2018, 10, 248.

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