Lung cancers: Molecular characterization, clonal heterogeneity and evolution, and cancer stem cells

Research output: Contribution to journalReview article

19 Citations (Scopus)

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.

Original languageEnglish
Article number248
JournalCancers
Volume10
Issue number8
DOIs
Publication statusPublished - Aug 1 2018

Fingerprint

Clonal Evolution
Neoplastic Stem Cells
Lung Neoplasms
Non-Small Cell Lung Carcinoma
Mutation
Neoplasms
Oncogene Fusion
High-Throughput Nucleotide Sequencing
Lung
Small Cell Lung Carcinoma
Phosphatidylinositol 3-Kinases
Oncogenes
Drug Resistance
Genes
Squamous Cell Carcinoma
Adenocarcinoma
Survival Rate
Clone Cells
Genome
Phenotype

Keywords

  • Cancer stem cells
  • Genomic profiling
  • Membrane cell markers
  • Non-small cell lung cancer
  • Small cell lung cancer
  • Tumor xenotransplantation assay

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Lung cancers : Molecular characterization, clonal heterogeneity and evolution, and cancer stem cells. / Testa, Ugo; Castelli, Germana; Pelosi, Elvira.

In: Cancers, Vol. 10, No. 8, 248, 01.08.2018.

Research output: Contribution to journalReview article

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