Detection of antimicrobial resistance via state-of-the-art technologies versus conventional methods DOI Creative Commons
Ayman Elbehiry, Eman Marzouk, Adil Abalkhail

et al.

Frontiers in Microbiology, Journal Year: 2025, Volume and Issue: 16

Published: Feb. 25, 2025

Antimicrobial resistance (AMR) is recognized as one of the foremost global health challenges, complicating treatment infectious diseases and contributing to increased morbidity mortality rates. Traditionally, microbiological culture susceptibility testing methods, such disk diffusion minimum inhibitory concentration (MIC) assays, have been employed identify AMR bacteria. However, these conventional techniques are often labor intensive time consuming lack requisite sensitivity for early detection resistance. Recent advancements in molecular genomic technologies-such next-generation sequencing (NGS), matrix-assisted laser desorption ionization-time flight mass spectrometry (MALDI-TOF MS), lateral flow immunoassays (LFIAs), PCR-based diagnostic CRISPR-based diagnostics-have revolutionized diagnosis AMR. These innovative approaches provide sensitivity, reduced turnaround times, ability genetic mechanisms. This review seeks examine advantages disadvantages both emerging technologies traditional methods detecting AMR, emphasizing potential benefits limitations inherent each. By understanding strengths technologies, stakeholders, including researchers, healthcare professionals, regulatory agencies, authorities, financial managers, patients, can make informed decisions aimed at preventing emergence dissemination antibiotic-resistant strains, thereby ultimately increasing patient safety.

Language: Английский

IL6 Mediates Suppression of T- and NK-cell Function in EMT-associated TKI-resistant EGFR-mutant NSCLC DOI
Sonia Patel, Monique B. Nilsson, Yan Yang

et al.

Clinical Cancer Research, Journal Year: 2023, Volume and Issue: 29(7), P. 1292 - 1304

Published: Jan. 3, 2023

Patients with advanced non-small cell lung cancer (NSCLC) harboring activating EGFR mutations are initially responsive to tyrosine kinase inhibitors (TKI). However, therapeutic resistance eventually emerges, often via secondary or EGFR-independent mechanisms such as epithelial-to-mesenchymal transition. Treatment options after EGFR-TKI limited anti-PD-1/PD-L1 typically display minimal benefit. Given that IL6 is associated worse outcomes in patients NSCLC, we investigate whether part contributes this immunosuppressed phenotype.We utilized a syngeneic genetically engineered mouse model (GEMM) of EGFR-mutant NSCLC the effects on tumor microenvironment and combined efficacy inhibition anti-PD-1 therapy. Corresponding vitro studies used human lines clinical specimens.We identified tumors which have oncogene-independent acquired EGFR-TKIs were more mesenchymal had markedly enhanced secretion. In GEMMs, depletion activation infiltrating natural killer (NK)- T-cell subpopulations decreased immunosuppressive regulatory T Th17 populations. Inhibition increased NK- cell-mediated killing osimertinib-resistant cells culture. blockade sensitized GEMM PD-1 through an increase tumor-infiltrating IFNγ+ CD8+ cells.These data indicate upregulated suppressed T- NK-cell function. antitumor immunity therapy warranting future combinatorial investigations.

Language: Английский

Citations

56
Trans-nuclease activity of Cas9 activated by DNA or RNA target binding DOI
Jiyun Chen, Ying Chen, Linglong Huang

et al.

Nature Biotechnology, Journal Year: 2024, Volume and Issue: unknown

Published: May 29, 2024

Language: Английский

Citations

24
The study of primary and acquired resistance to first-line osimertinib to improve the outcome of EGFR-mutated advanced Non-small cell lung cancer patients: the challenge is open for new therapeutic strategies DOI Creative Commons
Alessandra Ferro,

G.M. Marinato,

C. Mulargiu

et al.

Critical Reviews in Oncology/Hematology, Journal Year: 2024, Volume and Issue: 196, P. 104295 - 104295

Published: Feb. 20, 2024

The development of targeted therapy in epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC) patients has radically changed their clinical perspectives. Current first-line standard treatment for advanced disease is commonly considered third-generation tyrosine kinase inhibitors (TKI), osimertinib. study primary and acquired resistance to front-line osimertinib one the main burning issues further improve patients' outcome. Great heterogeneity been depicted terms duration benefit pattern progression this might be related molecular factors including subtypes EGFR mutations concomitant genetic alterations. Acquired can categorized into two classes: EGFR-dependent EGFR-independent mechanisms specific have demonstrated. purpose manuscript provide a comprehensive overview literature about osimertinib, from perspective therefore relationship emerging therapeutic approaches.

Language: Английский

Citations

23
The Role of TP53 Mutations in EGFR-Mutated Non-Small-Cell Lung Cancer: Clinical Significance and Implications for Therapy DOI Open Access
Matteo Canale, Kalliopi Andrikou,

Ilaria Priano

et al.

Cancers, Journal Year: 2022, Volume and Issue: 14(5), P. 1143 - 1143

Published: Feb. 23, 2022

Non-Small-Cell Lung Cancer (NSCLC) is the primary cause of cancer-related death worldwide. Oncogene-addicted patients usually benefit from targeted therapy, but and acquired resistance mechanisms inevitably occur. Tumor protein 53 (TP53) gene most frequently mutated in cancer, including NSCLC. TP53 mutations are able to induce carcinogenesis, tumor development influencing patient prognosis responsiveness therapy. mutants present different forms, suggesting that alterations confer specific functions. In recent years, many associations between responses Epidermal Growth Factor Receptor (EGFR) therapy NSCLC have been found. this review, we discuss current landscape concerning role guide Tyrosine-Kinase Inhibitors (TKIs) EGFR-directed, investigating possible within cellular compartments. We also predicting response with EGFR-TKIs, as a biomarker stratification for treatment.

Language: Английский

Citations

55
Regulation of Ferroptosis in Lung Adenocarcinoma DOI Open Access

Xiangyun Wei,

Xiaohe Li,

Shuming Hu

et al.

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(19), P. 14614 - 14614

Published: Sept. 27, 2023

Lung adenocarcinoma (LUAD) is the most common lung cancer, which accounts for about 35-40% of all cancer patients. Despite therapeutic advancements in recent years, overall survival time LUAD patients still remains poor, especially KRAS mutant LUAD. Therefore, it necessary to further explore novel targets and drugs improve prognos Ferroptosis, an iron-dependent regulated cell death (RCD) caused by lipid peroxidation, has attracted much attention recently as alternative target apoptosis therapy. Ferroptosis been found be closely related at every stage, including initiation, proliferation, progression. In this review, we will provide a comprehensive overview ferroptosis mechanisms, its regulation LUAD, application targeting

Language: Английский

Citations

34
The role of anti-EGFR therapies in EGFR-TKI-resistant advanced non-small cell lung cancer DOI Creative Commons
Fortunato Ciardiello, Fred R. Hirsch, Robert Pirker

et al.

Cancer Treatment Reviews, Journal Year: 2023, Volume and Issue: 122, P. 102664 - 102664

Published: Nov. 25, 2023

Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) are the current recommended option for first-line treatment of patients with EGFR-mutant non-small cell lung cancer (NSCLC). Resistance to first-generation TKIs led development second- and third-generation improved clinical outcomes. However, sequential administration has emergence new EGFR resistance mutations persistent tumor survival. This evidence highlights potential role in transducing signals NSCLC cells. Therefore, dual inhibition using combinations anti-EGFR monoclonal antibodies (mAbs) EGFR-TKIs may offer a unique strategy suppress growth. Several studies have demonstrated benefits blockade mAbs coupled overcoming EGFR-mutated NSCLC. single not result same all acquired resistance. Biomarkers, including overexpression, gene copy number, KRAS mutations, circulating DNA, been associated efficacy Further investigation biomarkers allow patient selection those who could benefit from combination EGFR-TKIs. review summarizes findings recent NSCLC, as well towards personalized targeted medicine.

Language: Английский

Citations

27
The role of selected non-coding RNAs in the biology of non-small cell lung cancer DOI Creative Commons
Kajetan Kiełbowski, Konrad Ptaszyński, Janusz Wójcik

et al.

Advances in Medical Sciences, Journal Year: 2023, Volume and Issue: 68(1), P. 121 - 137

Published: March 1, 2023

Lung cancer is the second most frequently diagnosed worldwide and a leading cause of cancer-related deaths. Non-small cell lung carcinoma (NSCLC) represents 85% all cases. Accumulating evidence highlights outstanding role non-coding RNA (ncRNA) in regulating tumorigenesis process by modulating crucial signaling pathways. Micro (miRNA), long (lncRNA) circular (circRNA) are either up- or downregulated patients can promote suppress progression disease. These molecules interact with messenger (mRNA) each other to regulate gene expression stimulate proto-oncogenes silence tumor suppressors. NcRNAs provide new strategy diagnose treat multiple have already been identified as potential biomarkers therapeutic targets. The aim this review summarize current on roles miRNA, lncRNA circRNA NSCLC biology present their clinical potential.

Language: Английский

Citations

26
The Resistance to EGFR-TKIs in Non-Small Cell Lung Cancer: From Molecular Mechanisms to Clinical Application of New Therapeutic Strategies DOI Creative Commons
Carmelo Laface,

Felicia Maria Maselli,

Anna Santoro

et al.

Pharmaceutics, Journal Year: 2023, Volume and Issue: 15(6), P. 1604 - 1604

Published: May 27, 2023

Almost 17% of Western patients affected by non-small cell lung cancer (NSCLC) have an activating epidermal growth factor receptor (EGFR) gene mutation. Del19 and L858R are the most-common ones; they positive predictive factors for EGFR tyrosine kinase inhibitors (TKIs). Currently, osimertinib, a third-generation TKI, is standard first-line therapy advanced NSCLC with common mutations. This drug also administered as second-line treatment those T790M mutation previously treated first- (erlotinib, gefitinib) or second- (afatinib) generation TKIs. However, despite high clinical efficacy, prognosis remains severe due to intrinsic acquired resistance EGRF-TKIs. Various mechanisms been reported including activation other signalling pathways, development secondary mutations, alteration downstream phenotypic transformation. further data needed achieve goal overcoming EGFR-TKIs, hence necessity discovering novel genetic targets developing new-generation drugs. review aimed deepen knowledge molecular EGFR-TKIs new therapeutic strategies overcome TKIs' resistance.

Language: Английский

Citations

23
NEAT1_1 confers gefitinib resistance in lung adenocarcinoma through promoting AKR1C1-mediated ferroptosis defence DOI Creative Commons

Shuman Zhen,

Yunlong Jia, Yan Zhao

et al.

Cell Death Discovery, Journal Year: 2024, Volume and Issue: 10(1)

Published: March 12, 2024

Abstract Gefitinib is one of the most extensively utilized epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) for treating advanced lung adenocarcinoma (LUAD) patients harboring EGFR mutation. However, emergence drug resistance significantly compromised clinical efficacy EGFR-TKIs. Gaining further insights into molecular mechanisms underlying gefitinib holds promise developing novel strategies to overcome and improve prognosis in LUAD patients. Here, we identified that inhibitory on EGFR-mutated cells was partially dependent induction ferroptosis, ferroptosis protection resulted resistance. Among suppressors, aldo-keto reductase family 1 member C1 (AKR1C1) exhibited significant upregulation gefitinib-resistant strains predicted poor progression-free survival (PFS) overall (OS) who received first-generation EGFR-TKI treatment. Knockdown AKR1C1 reversed by re-sensitizing gefitinib-mediated ferroptosis. The decreased expression miR-338-3p contributed aberrant cells. Furthermore, upregulated long non-coding RNA (lncRNA) nuclear paraspeckle assembly transcript 1_1 (NEAT1_1) sponged neutralize its suppression AKR1C1. Dual-luciferase reporter assay miRNA rescue experiment confirmed NEAT1_1/miR-338-3p/AKR1C1 axis Gain- loss-of-function assays demonstrated promoted resistance, proliferation, migration, invasion This study reveals effects axis-mediated defence LUAD. Thus, targeting might be a strategy overcoming

Language: Английский

Citations

13
The emerging landscape and future perspective of SCLC transformation: from molecular mechanisms to therapeutic strategies DOI
Chenyue Zhang, Kai Wang, Haiyong Wang

et al.

Critical Reviews in Oncology/Hematology, Journal Year: 2025, Volume and Issue: 207, P. 104616 - 104616

Published: Jan. 11, 2025

Language: Английский

Citations

1