Driver genes in non-small cell lung cancer: Characteristics, detection methods, and targeted therapies

Zhu, Qing-Ge; Zhang, Shiming; Ding, Xiaoxiao; He, Bing; Zhang, Huqin

doi:10.18632/oncotarget.17016

Cited by 73 publications

(58 citation statements)

References 86 publications

(87 reference statements)

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“…We identified that IGF2BP2 rs4402960 T allele might probably be a protective factor for NSCLC, which was not consistent with the findings of previous studies. It is believed that there are some LC-related driver genes possessing low frequency variant, which modify the states of chromatin or DNA 37. In addition, intronic region could bind to some proteins and even directly alter special gene transcription 37–39.…”

Section: Discussionmentioning

confidence: 99%

Relationship between IGF2BP2 and IGFBP3 polymorphisms and susceptibility to non-small-cell lung cancer: a case–control study in Eastern Chinese Han population

Chen

Qiu

Liu

et al. 2018

CMAR

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BackgroundIGF2BP2 and IGFBP3 polymorphisms may be associated with cancer risk.MethodsWith an aim to determine the association of variations in IGF2BP2 and IGFBP3 genes with risk of non-small-cell lung cancer (NSCLC), IGF2BP2 rs1470579 A>C, rs4402960 G>T and IGFBP3 rs2270628 C>T, rs3110697 G>A, and rs6953668 G>A polymorphisms were selected and genotyped in 521 NSCLC patients and 1,030 controls.ResultsWe found that there was no difference in IGF2BP2 and IGFBP3 genotype distribution among the NSCLC patients and controls. The stratified analyses suggested that IGF2BP2 rs1470579 A>C polymorphism decreased the risk of NSCLC in some subgroups (female subgroup: CC vs AA: adjusted P=0.032 and CC vs AC/AA: adjusted P=0.028; <60 years subgroup: CC vs AA: adjusted P=0.012 and CC vs AC/AA: adjusted P=0.013; and never drinking subgroup: CC vs AA: adjusted P=0.046 and CC vs AC/AA: adjusted P=0.031). The stratified analyses also found that IGF2BP2 rs4402960 G>T polymorphism decreased the risk of NSCLC in some subgroups (female subgroup: TT vs GG: adjusted P=0.031 and TT vs GT/GG: adjusted P=0.026; <60 subgroup: TT vs GG: adjusted P=0.037 and TT vs GT/GG: adjusted P=0.038; and never drinking subgroup: TT vs GT/GG: adjusted P=0.046). Haplotype analysis indicated Ars1470579Crs2270628Grs3110697Grs4402960Ars6953668 haplotype decreased susceptibility of NSCLC (P=0.007).ConclusionOur study suggests that IGF2BP2 rs1470579 A>C, rs4402960 G>T single-nucleotide polymorphisms are candidates for decreased susceptibility to NSCLC among female, <60 years, and never drinking subgroups. In the future, more case–control studies with functional analysis are needed to confirm these preliminary findings.

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Section: Discussionmentioning

confidence: 99%

Relationship between IGF2BP2 and IGFBP3 polymorphisms and susceptibility to non-small-cell lung cancer: a case–control study in Eastern Chinese Han population

Chen

Qiu

Liu

et al. 2018

CMAR

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“…Particularly, these TK inhibitors generate high response rates and significant survival benefits in tumors carrying a somatic mutation in the TK receptor targeted by the TK inhibitor. The identification of actionable driver mutations in these receptors, including EGFR , ALK , ROS , BRAF and ERBB2 mutations, combined with the decreasing cost of genomic testing was key for the clinical implementation of these treatments . However, all NSCLC tumors at some point acquire resistance to these treatments.…”

Section: Introductionmentioning

confidence: 99%

“…The identification of actionable driver mutations in these receptors, including EGFR, ALK, ROS, BRAF and ERBB2 mutations, combined with the decreasing cost of genomic testing was key for the clinical implementation of these treatments. 10 However, all NSCLC tumors at some point acquire resistance to these treatments.…”

Section: Introductionmentioning

confidence: 99%

The genomic landscape of nonsmall cell lung carcinoma in never smokers

Boeckx

Shahi

Smeets

et al. 2019

Intl Journal of Cancer

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Lung cancer is the number one cause of cancer‐related death worldwide with cigarette smoking as its major risk factor. Although the incidence of lung cancer in never smokers is rising, this subgroup of patients is underrepresented in genomic studies of lung cancer. Here, we assembled a prospective cohort of 46 never‐smoking, nonsmall cell lung cancer (NSCLC) patients and performed whole‐exome and low‐coverage whole‐genome sequencing on tumors and matched germline DNA. We observed fewer somatic mutations, genomic breakpoints and a smaller fraction of the genome with chromosomal instability in lung tumors from never smokers compared to smokers. The lower number of mutations, enabled us to identify TSC22D1 as a potential driver gene in NSCLC. On the other hand, the frequency of mutations in actionable genes such as EGFR and ERBB2 and of amplifications in MET were higher, while the mutation rate of TP53, which is a negative prognostic factor, was lower in never smokers compared to smokers. Together, these observations suggest a more favorable prognosis for never smokers with NSCLC. Classification of somatic mutations into six‐substitution type patterns or into 96‐substitution type signatures revealed distinct clusters between smokers and never smokers. Particularly, we identified in never smokers signatures related to aging, homologous recombination damage and APOBEC/AID activity as the most important underlying processes of NSCLC. This further indicates that second‐hand smoking is not driving NSCLC pathogenesis in never smokers.

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“…Non‐small cell lung cancer (NSCLC) accounts for over 85% of lung cancer diagnoses and most patients present with advanced stage at the time of diagnosis . Current standard first‐line treatment for advanced NSCLC is platinum‐based doublet chemotherapy when no targetable alterations, such as EGFR mutations or ALK or ROS1 rearrangements, are detected in genomic testing .…”

Section: Introductionmentioning

confidence: 99%

Real world study of regimen containing bevacizumab as first‐line therapy in Chinese patients with advanced non‐small cell lung cancer

Xing

Wang

et al. 2018

Thoracic Cancer

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BackgroundLarge scale randomized controlled trials have demonstrated that the use of bevacizumab in addition to chemotherapy in patients with advanced non‐small cell lung cancer (NSCLC) conveys significant survival benefits. We explored the clinical impact of a first‐line regimen containing bevacizumab (B+) versus a non‐bevacizumab regimen (non‐B) in advanced non‐squamous NSCLC (NS‐NSCLC) patients in a real world setting.MethodsThe medical records of patients with advanced NS‐NSCLC who received first‐line therapy with or without bevacizumab were retrospectively collected. The primary outcome was progression‐free survival (PFS), with secondary objectives of objective response rate (ORR), disease control rate (DCR), and safety. Exploratory analysis of EGFR and ALK status was conducted in subgroup.ResultsOne hundred and forty‐nine patients met the selection criteria: 62 in the B+ and 87 in the non‐B group. The baseline characteristics were well balanced. In the overall population, the median PFS was significantly longer in the B+ than in the non‐B group (9.7 vs. 7.0 months, hazard ratio [HR] 0.52, 95% confidence interval [CI] 0.30–0.91; P = 0.0184). Improved trends in both ORR and DCR were observed in the B+ group. In wild‐type patients, the median PFS of the B+ was 11.3 compared to 5.5 months in the non‐B group (HR 0.43, 95% CI 0.20–0.91; P = 0.0234). In wild type and unknown populations, the median PFS was 11.3 (B+) compared to 6.0 months (non‐B) (HR 0.53; 95% CI 0.28–1.02; P = 0.0520). The safety profile was acceptable in both groups and no unexpected findings were observed.ConclusionOur analysis confirmed that a first‐line regimen containing bevacizumab showed superior clinical benefits over a non‐bevacizumab regimen in Chinese patients with advanced NS‐NSCLC in a real world setting.

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Driver genes in non-small cell lung cancer: Characteristics, detection methods, and targeted therapies

Cited by 73 publications

References 86 publications

Relationship between <em>IGF2BP2</em> and <em>IGFBP3</em> polymorphisms and susceptibility to non-small-cell lung cancer: a case–control study in Eastern Chinese Han population

Relationship between <em>IGF2BP2</em> and <em>IGFBP3</em> polymorphisms and susceptibility to non-small-cell lung cancer: a case–control study in Eastern Chinese Han population

The genomic landscape of nonsmall cell lung carcinoma in never smokers

Real world study of regimen containing bevacizumab as first‐line therapy in Chinese patients with advanced non‐small cell lung cancer

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Driver genes in non-small cell lung cancer: Characteristics, detection methods, and targeted therapies

Cited by 73 publications

References 86 publications

Relationship between <em>IGF2BP2</em> and <em>IGFBP3</em> polymorphisms and susceptibility to non-small-cell lung cancer: a case&ndash;control study in Eastern Chinese Han population

Relationship between <em>IGF2BP2</em> and <em>IGFBP3</em> polymorphisms and susceptibility to non-small-cell lung cancer: a case&ndash;control study in Eastern Chinese Han population

The genomic landscape of nonsmall cell lung carcinoma in never smokers

Real world study of regimen containing bevacizumab as first‐line therapy in Chinese patients with advanced non‐small cell lung cancer

Contact Info

Product

Resources

About

Relationship between <em>IGF2BP2</em> and <em>IGFBP3</em> polymorphisms and susceptibility to non-small-cell lung cancer: a case–control study in Eastern Chinese Han population

Relationship between <em>IGF2BP2</em> and <em>IGFBP3</em> polymorphisms and susceptibility to non-small-cell lung cancer: a case–control study in Eastern Chinese Han population