Non–Small Cell Lung Cancer and Precision Medicine

Pasche, Boris; Grant, Stefan C.

doi:10.1001/jama.2014.3742

Cited by 31 publications

(14 citation statements)

References 16 publications

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“…Generally biomarkers indicate the turbulence in the normal biological status that contributes to carcinogenesis. Currently, a number of biomarkers, mostly from circulating cells, are used in diagnosing cancer [ 15 - 19 ], epidemiology [ 20 - 23 ], and treatment follow up [ 24 - 26 ]. Many of the existing biomarkers offer insufficient information about the tissue origin and thus it is difficult to use them in targeted therapy [ 16 ].…”

Section: Introductionmentioning

confidence: 99%

Extracellular vesicles: potential applications in cancer diagnosis, prognosis, and epidemiology

et al. 2015

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Both normal and diseased cells continuously shed extracellular vesicles (EVs) into extracellular space, and the EVs carry molecular signatures and effectors of both health and disease. EVs reflect dynamic changes that are occurring in cells and tissue microenvironment in health and at a different stage of a disease. EVs are capable of altering the function of the recipient cells. Trafficking and reciprocal exchange of molecular information by EVs among different organs and cell types have been shown to contribute to horizontal cellular transformation, cellular reprogramming, functional alterations, and metastasis. EV contents may include tumor suppressors, phosphoproteins, proteases, growth factors, bioactive lipids, mutant oncoproteins, oncogenic transcripts, microRNAs, and DNA sequences. Therefore, the EVs present in biofluids offer unprecedented, remote, and non-invasive access to crucial molecular information about the health status of cells, including their driver mutations, classifiers, molecular subtypes, therapeutic targets, and biomarkers of drug resistance. In addition, EVs may offer a non-invasive means to assess cancer initiation, progression, risk, survival, and treatment outcomes. The goal of this review is to highlight the current status of information on the role of EVs in cancer, and to explore the utility of EVs for cancer diagnosis, prognosis, and epidemiology.

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Section: Introductionmentioning

confidence: 99%

Extracellular vesicles: potential applications in cancer diagnosis, prognosis, and epidemiology

et al. 2015

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“…Oncogenic ALK and ROS1 fusion-targeted therapy using type I tyrosine-kinase inhibitors (TKIs), which bind to the ATP-binding cleft of kinases, is highly effective in lung adenocarcinoma (LADC) 1 , 2 ; however, such cancers inevitably acquire resistance to targeted therapies, which severely limits the efficacy of cancer treatments. Secondary mutations that cause amino acid substitutions in the kinase domain (KD), including the gatekeeper and solvent-accessible regions, are an important cause of resistance to various extents 3 .…”

Section: Introductionmentioning

confidence: 99%

A secondary RET mutation in the activation loop conferring resistance to vandetanib

Nakaoku¹,

Kohno²,

Araki

et al. 2018

Nat Commun

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Resistance to vandetanib, a type I RET kinase inhibitor, developed in a patient with metastatic lung adenocarcinoma harboring a CCDC6-RET fusion that initially exhibited a response to treatment. The resistant tumor acquired a secondary mutation resulting in a serine-to-phenylalanine substitution at codon 904 in the activation loop of the RET kinase domain. The S904F mutation confers resistance to vandetanib by increasing the ATP affinity and autophosphorylation activity of RET kinase. A reduced interaction with the drug is also observed in vitro for the S904F mutant by thermal shift assay. A crystal structure of the S904F mutant reveals a small hydrophobic core around F904 likely to enhance basal kinase activity by stabilizing an active conformer. Our findings indicate that missense mutations in the activation loop of the kinase domain are able to increase kinase activity and confer drug resistance through allosteric effects.

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“…Small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC) are the most common types of lung cancer, of which NSCLC accounts for approximately 85% of all cases ( 1 ). Lung adenocarcinoma is the most common subtype of NSCLC (40%) in many countries ( 2 , 3 ). To date, many genetic factors have been proposed to be involved in lung adenocarcinoma, including several tumour-suppressor genes (TP53, CDKN2A, STK11, NF1, ATM, RB1, and APC) ( 4 , 5 ).…”

Section: Introductionmentioning

confidence: 99%

Meta-analysis of mRNA expression profiles to identify differentially expressed genes in lung adenocarcinoma tissue from smokers and non-smokers

Zhang

Shi

et al. 2018

Oncol Rep

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Compared to other types of lung cancer, lung adenocarcinoma patients with a history of smoking have a poor prognosis during the treatment of lung cancer. How lung adenocarcinoma-related genes are differentially expressed between smoker and non-smoker patients has yet to be fully elucidated. We performed a meta-analysis of four publicly available microarray datasets related to lung adenocarcinoma tissue in patients with a history of smoking using R statistical software. The top 50 differentially expressed genes (DEGs) in smoking vs. non-smoking patients are shown using heat maps. Additionally, we conducted KEGG and GO analyses. In addition, we performed a PPI network analysis for 8 genes that were selected during a previous analysis. We identified a total of 2,932 DEGs (1,806 upregulated, 1,126 downregulated) and five genes (CDC45, CDC20, ANAPC7, CDC6, ESPL1) that may link lung adenocarcinoma to smoking history. Our study may provide new insights into the complex mechanisms of lung adenocarcinoma in smoking patients, and our novel gene expression signatures will be useful for future clinical studies.

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Non–Small Cell Lung Cancer and Precision Medicine

Cited by 31 publications

References 16 publications

Extracellular vesicles: potential applications in cancer diagnosis, prognosis, and epidemiology

Extracellular vesicles: potential applications in cancer diagnosis, prognosis, and epidemiology

A secondary RET mutation in the activation loop conferring resistance to vandetanib

Meta-analysis of mRNA expression profiles to identify differentially expressed genes in lung adenocarcinoma tissue from smokers and non-smokers

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