Targeted drug therapy in non-small cell lung cancer: Clinical significance and possible solutions-Part I

Upadhya, Archana; Yadav, Khushwant S.; Misra, Ambikanandan

doi:10.1080/17425247.2021.1825377

Cited by 15 publications

(6 citation statements)

References 280 publications

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“…55 Targeting NTRK1 fusion proteins have been proposed as a promising strategy to overcome NTRK1-mediated drug resistance in NSCLC. [56][57][58][59][60] These evidences are in agreement with our findings and suggest NTRK1 as a potential target of cisplatin resistance in NSCLC, although further studies are needed on this gene in lung cancer.…”

Section: Discussionsupporting

confidence: 91%

Meta‐analysis of microarray data to determine gene indicators involved in cisplatin resistance in non‐small cell lung cancer

Sheikhshabani,

Modarres,

Ghafouri‐Fard

et al. 2024

Cancer Reports

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BackgroundLung cancer is a major cause of cancer‐related mortality worldwide, with a 5‐year survival rate of approximately 22%. Cisplatin is one of the standard first‐line chemotherapeutic agents for non‐small cell lung cancer (NSCLC), but its efficacy is often limited by the development of resistance. Despite extensive research on the molecular mechanisms of chemoresistance, the underlying causes remain elusive and complex.AimsWe analyzed three microarray datasets to find the gene signature and key pathways related to cisplatin resistance in NSCLC.Methods and ResultsWe compared the gene expression of sensitive and resistant NSCLC cell lines treated with cisplatin. We found 274 DEGs, including 111 upregulated and 163 downregulated genes, in the resistant group. Gene set enrichment analysis showed the potential roles of several DEGs, such as TUBB2B, MAPK7, TUBAL3, MAP2K5, SMUG1, NTHL1, PARP3, NTRK1, G6PD, PDK1, HEY1, YTHDF2, CD274, and MAGEA1, in cisplatin resistance. Functional analysis revealed the involvement of pathways, such as gap junction, base excision repair, central carbon metabolism, and Notch signaling in the resistant cell lines.ConclusionWe identified several molecular factors that contribute to cisplatin resistance in NSCLC cell lines, involving genes and pathways that regulate gap junction communication, DNA damage repair, ROS balance, EMT induction, and stemness maintenance. These genes and pathways could be targets for future studies to overcome cisplatin resistance in NSCLC.

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Section: Discussionsupporting

confidence: 91%

Meta‐analysis of microarray data to determine gene indicators involved in cisplatin resistance in non‐small cell lung cancer

Sheikhshabani,

Modarres,

Ghafouri‐Fard

et al. 2024

Cancer Reports

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“…Targeted therapy has been approved to combine with traditional therapy. In a variety of cancers, combined targeted therapy shows better anti-cancer effect (28)(29)(30). Therefore, we studied the efficacy of targeted therapy based on radiotherapy and temozolomidebased chemotherapy.…”

Section: Discussionmentioning

confidence: 99%

The efficacy of targeted therapy combined with radiotherapy and temozolomide-based chemotherapy in the treatment of glioma: A systemic review and meta-analysis of phase II/III randomized controlled trials

Wang

Nie

et al. 2023

Front. Oncol.

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BackgroundGlioma is the most common intracranial tumor, accounting for about half of the primary intracranial tumors, with the characteristics of hidden onset and high mortality. Even after surgery, radiotherapy and chemotherapy, the prognosis of glioma is not ideal. Targeted therapy has developed rapidly in the treatment of other malignant tumors, which is also an important direction in the research and development of new therapies for glioma. So far, targeting combined with radiotherapy and chemotherapy have been used as the treatment of glioma in many clinical trials, but the role of targeted combined radiotherapy and chemotherapy in the treatment of glioma is still controversial. The purpose of this study was to evaluate the efficacy of targeted therapy combined with radiotherapy and temozolomide (TMZ)-based chemotherapy in the treatment of glioma.MethodsPhase II or phase III clinical trials involving targeted therapy combined with radiotherapy and chemotherapy and temozolomide-based radiotherapy and chemotherapy for gliomas were searched using PubMed, Embase and Web of Science databases, and a comprehensive meta-analysis was conducted. The primary outcome was overall survival time (OS) and progression-free survival time (PFS), and the secondary outcome was adverse reaction. The time-to-event data is summarized as hazard ratio (HR), and the binary results are summarized as odds ratio (OR). Two researchers conducted literature screening, data extraction and quality evaluation according to inclusion and exclusion criteria. Stata16.0 software was used for analysis, random effect model was used for data merging, and forest map was used for display.ResultsA total of 11 eligible literatures and 12 prospective randomized controlled clinical trials of 1284 cases were included in the meta-analysis. The results showed that compared with radiotherapy and chemotherapy alone, targeted drugs combined with temozolomide-based radiotherapy and chemotherapy could significantly improve OS in phase II trial, but there was no improvement in Phase III trial, and PFS of newly diagnosed glioma patients was improved (HR=0.82(0.71-0.94) 95%CI, p =0.005). The PFS of the third phase of the experiment also improved. Compared with radiotherapy and chemotherapy alone, there was no statistically significant increase in adverse events in targeted combined radiotherapy and chemotherapy group.Systematic review registrationhttps://www.crd.york.ac.uk/prospero, identifier CRD42022326012.

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“…The process of NSCLC development is complex and diverse, involving multiple signaling pathways, such as PI3K/Akt signaling pathway, human matrix metalloproteinase 9 (MMP9), cell cycle protein-dependent kinase 1 (CDK1), and Wnt/β-catenin signaling pathway [3][4][5][6]. According to recent research results, the treatment of NSCLC is mainly based on Western medicine, including surgery, chemotherapy, radiotherapy, targeted therapy, and immunotherapy [7,8]. However, these treatments are often accompanied by undesirable consequences such as susceptibility to recurrence and metastasis, poor prognosis, and high costs [9].…”

Section: Introductionmentioning

confidence: 99%

The Effect of Citrus aurantium on Non‐Small‐Cell Lung Cancer: A Research Based on Network and Experimental Pharmacology

Yao

Zhang

Huang

et al. 2023

BioMed Research International

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Purpose. To screen the main active components of Citrus aurantium through a network pharmacology approach, construct a component-disease target network, explore its molecular mechanism for the treatment of non-small-cell lung cancer (NSCLC), and validate it experimentally. Methods. The active ingredients in Citrus aurantium and the targets of Citrus aurantium and NSCLC were collected through the Traditional Chinese Medicine Systematic Pharmacology Database and Analysis Platform (TCMSP), GeneCards, and OMIM databases. The protein interaction network was constructed using the STRING database, and the component-disease relationship network graph was analyzed using Cytoscape 3.9.1. The Metascape database can be used for GO and KEGG enrichment analyses. The Kaplan-Meier plotter was applied for overall survival analysis of key targets of Citrus aurantium in the treatment of NSCLC. Real-time PCR (RT-PCR) and Western blotting were used to determine the mRNA and protein levels of key targets of Citrus aurantium for the treatment of NSCLC. Results. Five active ingredients of Citrus aurantium were screened, and 54 potential targets for the treatment of NSCLC were found, of which the key ingredient was nobiletin and the key targets are TP53, CXCL8, ESR1, PPAR-α, and MMP9. GO and KEGG enrichment analyses indicated that the mechanism of nobiletin in treating NSCLC may be related to the regulation of cancer signaling pathway, phosphatidylinositol-3 kinase (PI3K)/protein kinase B (Akt) signaling pathway, lipid and atherosclerosis signaling pathway, and neurodegenerative signaling pathway. The experimental results showed that nobiletin could inhibit the proliferation of NSCLC cells and upregulate the levels of P53 and PPAR-α and suppress the expression of MMP9 ( P < 0.05 ). Conclusion. Citrus aurantium can participate in the treatment of NSCLC through multiple targets and pathways.

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Targeted drug therapy in non-small cell lung cancer: Clinical significance and possible solutions-Part I

Cited by 15 publications

References 280 publications

Meta‐analysis of microarray data to determine gene indicators involved in cisplatin resistance in non‐small cell lung cancer

Meta‐analysis of microarray data to determine gene indicators involved in cisplatin resistance in non‐small cell lung cancer

The efficacy of targeted therapy combined with radiotherapy and temozolomide-based chemotherapy in the treatment of glioma: A systemic review and meta-analysis of phase II/III randomized controlled trials

The Effect of Citrus aurantium on Non‐Small‐Cell Lung Cancer: A Research Based on Network and Experimental Pharmacology

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