Targeted therapy in non-small cell lung cancer

Putora, Paul Martin; Schneider, Tino; Rodriguez, Regulo; Früh, Martin

doi:10.1183/20734735.021511

Cited by 6 publications

(7 citation statements)

References 31 publications

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“…Some of these mutations improve tyrosine kinase activity and so sensitivity to targeted therapy, whereas others increase cell resistance to treatment with tyrosine kinase inhibitors (TKIs). 15 F I G U R E 6 Common target genes from different disease pathways and network clusters. This analysis revealed PIK3CA, BRAF and EGFR are the most important target genes for the therapeutic use of non-small cell lung cancer (NSCLC).…”

Section: Disease Enrichment Pathway Analysis Of Clustered Genesmentioning

confidence: 99%

“…The tyrosine kinase, which is located inside the cell, is responsible for signal transduction, whereas ligand binding occurs on the extracellular region of the receptor. 15 The extracellular receptor is activated by dimerisation following the binding of a ligand, such as epidermal growth factor (EGF) or transforming growth factor-a (TGF-a). The signal travels through a number of downstream routes.…”

Section: Disease Enrichment Pathway Analysis Of Clustered Genesmentioning

confidence: 99%

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Identifying druggable targets from active constituents of Azadirachta indica A. Juss. for non‐small cell lung cancer using network pharmacology and validation through molecular docking

Nath

Baishya

Nath³

et al. 2023

Phytochemical Analysis

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IntroductionAzadirachta indica A. Juss. is a well‐known medicinal plant that has been used traditionally to cure various ailments in every corner of the globe. There are many in vitro and in vivo experimental evidences in connection with the bioactivity of the extracts of this plant. Lung cancer is the deadliest form of cancer and contributes to the most cancer related deaths. The mode of action of anticancer components of this plant is still to be established explicitly.ObjectiveThe objective of this study is to identify druggable targets of active constituents of A. indica A. Juss. for non‐small cell lung cancer (NSCLC) using network pharmacology and validation of activity through molecular docking analysis.MethodologyTargets of all the active phytochemicals from A. indica were predicted and genes related to NSCLC were retrieved. A protein–protein interaction (PPI) network of the overlapping genes were prepared. Various databases and servers were employed to analyse the disease pathway enrichment analysis of the clustered genes. Validation of the gene/protein activity was achieved by performing molecular docking, and ADMET profiling of selected phytocompounds was performed.ResultGene networking revealed three key target genes as EGFR, BRAF and PIK3CA against NSCLC by the active components of A. indica. Molecular docking and ADMET analysis further validated that desacetylnimbin, nimbandiol, nimbin, nimbinene, nimbolide, salannin and vepinin are the best suited anti‐ NSCLC among all the phytocompounds present in this plant.ConclusionThe present study has provided a better understanding of the pharmacological effects of active components from A. indica and its potential therapeutic effect on NSCLC.

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Section: Disease Enrichment Pathway Analysis Of Clustered Genesmentioning

confidence: 99%

Section: Disease Enrichment Pathway Analysis Of Clustered Genesmentioning

confidence: 99%

Identifying druggable targets from active constituents of Azadirachta indica A. Juss. for non‐small cell lung cancer using network pharmacology and validation through molecular docking

Nath

Baishya

Nath³

et al. 2023

Phytochemical Analysis

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“…In recent years, the emergence of new therapies targeting signaling pathways activated by genetic changes has revolutionized the treatment of non-small cell lung cancer (NSCLC), particularly adenocarcinoma [2]. Anaplastic lymphoma kinase (ALK) rearrangement and epidermal growth factor receptor (EGFR) mutation are important subtypes in NSCLC targeted by tyrosine kinase inhibitors (TKIs) [3]. Treatment with TKIs has shown longer progression-free survival (PFS) compared to conventional chemotherapy in these subtypes seen in NSCLC [4].…”

Section: Introductionmentioning

confidence: 99%

IMPORTANCE of PRETREATMENT 18F-FDG PET/CT TEXTURE ANALYSIS in PREDICTING EGFR and ALK MUTATION in PATIENTS with NON-SMALL CELL LUNG CANCER

Agüloğlu¹,

Aksu

Akyol³

et al. 2022

Nuklearmedizin

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Objective Identification of anaplastic lymphoma kinase (ALK) and epidermal growth factor receptor (EGFR) mutation types is of great importance before treatment with tyrosine kinase inhibitors (TKIs). Radiomics is a new strategy for noninvasively predicting the genetic status of cancer. We aimed to evaluate the predictive power of 18F-FDG PET/CT-based radiomic features for mutational status before treatment in non-small cell lung cancer (NSCLC) and to develop a predictive model based on radiomic features. Methods Images of patients who underwent 18F-FDG PET/CT for initial staging with the diagnosis of NSCLC between January 2015 and July 2020 were evaluated using LIFEx software. The region of interest (ROI) of the primary tumor was established and volumetric and textural features were obtained. Clinical data and radiomic data were evaluated with machine learning (ML) algorithms to create a model. Results For EGFR mutation prediction, the most successful machine learning algorithm obtained with GLZLM_GLNU and clinical data was Naive Bayes (AUC: 0.751, MCC: 0.347, acc: 71.4%). For ALK rearrangement prediction, the most successful machine learning algorithm obtained with GLCM_correlation, GLZLM_LZHGE and clinical data was evaluated as Naive Bayes (AUC: 0.682, MCC: 0.221, acc: 77.4%). Conclusions In our study, we created prediction models based on radiomic analysis of 18F-FDG PET/CT images. Tissue analysis with ML algorithms are non-invasive methods for predicting ALK rearrangement and EGFR mutation status in NSCLC, which may be useful for targeted therapy selection in a clinical setting.

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“…Treatment options for NSCLC have improved greatly in recent years with the advancement in treatments that are targeted against mutated genes, such as epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK), ROS proto-oncogene 1 (ROS-1) and v-raf murine sarcoma viral oncogene homolog B1(BRAF) [3][4][5][6]. Types with ALK rearrangement and EGFR mutation represent important subtypes of NSCLC targeted by tyrosine kinase inhibitors (TKI) [7]. ALK mutation detection is widely used clinically for NSCLC patients [8].…”

Section: Introductionmentioning

confidence: 99%

The prognostic relationship of 18F-FDG PET/CT metabolic and volumetric parameters in metastatic ALK + NSCLC

Agüloğlu¹,

Aksu²,

Unat³

et al. 2022

Nuclear Medicine Communications

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Objective The aim of this study is to determine the role of metabolic and volumetric parameters obtained from 18Fluorine-Fluorodeoxyglucose PET/computed tomography (18F-FDG PET/CT) imaging on progression-free survival (PFS) and overall survival (OS) in patients with advanced nonsquamous cell lung carcinoma (NSCLC) with anaplastic lymphoma kinase (ALK) rearrangement. Methods Pre and post-treatment PET/CT images of the ALK + NSCLC patients between January 2015 and July 2020 were evaluated. The highest standardized uptake value (SUVmax), metabolic tumor volume (MTV) and total lesion glycolysis (TLG) values were obtained from pre-tyrosine kinase inhibitor (TKI) basal PET/CT (PETpre) and post-TKI PET/CT (PETpost) images. Total MTV (tMTV) and total TLG (tTLG) values were calculated by summing MTV and TLG values in all tumor foci. The change (Δ) in pSUVmax, pMTV, pTLG, tMTV and tTLG before and after treatment was calculated.The relationship of these parameters with OS and PFS was analyzed. Results tTLGpre, tMTVpre, pTLGpre, pMTVpre, ∆SUVmax, ∆tMTV and ∆tTLG values were found to be associated with OS; ∆tMTV, ∆tTLG, tTLGpre, tMTVpre, pTLGpre and pMTVpre were associated with PFS. The cutoff values in both predicting OS and PFS were calculated as −31.6 and 391.1 for ∆tMTV and tTLGpre, respectively. In Cox regression analysis, ∆tMTV and stage for OS and ∆tMTV and tTLGpre for PFS were obtained as prognostic factors. Conclusions Metabolic and volumetric parameters, especially TLG values in the whole body before treatment and change in whole body MTV value, obtained from PET/CT may be useful in predicting prognosis and determining treatment strategies for patients with advanced ALK + NSCLC.

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Targeted therapy in non-small cell lung cancer

Abstract: Educational aimsTo explain the clinically relevant molecular pathways in lung cancer.To understand the basic principles of tests useful for targeted therapies.To present a basis for current treatment approaches.

Cited by 6 publications

References 31 publications

Identifying druggable targets from active constituents of Azadirachta indica A. Juss. for non‐small cell lung cancer using network pharmacology and validation through molecular docking

Identifying druggable targets from active constituents of Azadirachta indica A. Juss. for non‐small cell lung cancer using network pharmacology and validation through molecular docking

IMPORTANCE of PRETREATMENT 18F-FDG PET/CT TEXTURE ANALYSIS in PREDICTING EGFR and ALK MUTATION in PATIENTS with NON-SMALL CELL LUNG CANCER

The prognostic relationship of 18F-FDG PET/CT metabolic and volumetric parameters in metastatic ALK + NSCLC

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