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

Targeting the Tumor Microenvironment in EGFR-Mutant Lung Cancer: Opportunities and Challenges DOI Creative Commons
Jeong Uk Lim, Junyang Jung, Yeon Wook Kim

et al.

Biomedicines, Journal Year: 2025, Volume and Issue: 13(2), P. 470 - 470

Published: Feb. 14, 2025

Tyrosine kinase inhibitors (TKIs) have transformed the treatment of epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer. However, resistance remains a major challenge in clinical practice. The tumor microenvironment (TME) is complex system composed cells, immune and non-immune non-cellular components. Evidence indicates that dynamic changes TME during TKI are associated with development resistance. Research has focused on identifying how each component interacts tumors TKIs to understand therapeutic targets could address In this review, we describe components, such as fibroblasts, blood vessels, checkpoint proteins, cytokines, interact EGFR-mutant they can promote TKIs. Furthermore, discuss potential strategies targeting novel approach.

Language: Английский

Citations

1
New update to the guidelines on testing predictive biomarkers in non-small-cell lung cancer: a National Consensus of the Spanish Society of Pathology and the Spanish Society of Medical Oncology DOI Creative Commons
Dolores Isla, María D. Lozano, Luís Paz-Ares

et al.

Clinical & Translational Oncology, Journal Year: 2022, Volume and Issue: 25(5), P. 1252 - 1267

Published: Dec. 26, 2022

Non-small cell lung cancer (NSCLC) presents the greatest number of identified therapeutic targets, some which have utility. Currently, detecting EGFR, BRAF, KRAS and MET mutations, ALK, ROS1, NTRK RET translocations, PD-L1 expression in these patients is considered essential. The use next-generation sequencing facilitates precise molecular diagnosis allows detection other emerging such as HER2 mutation predictive biomarkers for immunotherapy responses. In this consensus, a group experts treatment NSCLC selected by Spanish Society Pathology Medical Oncology evaluated currently available information propose series recommendations to optimize daily clinical practice.

Language: Английский

Citations

31
Multimodal scanning of genetic variants with base and prime editing DOI Creative Commons
Olivier Belli, Kyriaki Karava, Rick Farouni

et al.

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

Published: Nov. 12, 2024

Mutational scanning connects genetic variants to phenotype, enabling the interrogation of protein functions, interactions and variant pathogenicity. However, current methodologies cannot efficiently engineer customizable sets diverse in endogenous loci across cellular contexts high throughput. Here, we combine cytosine adenine base editors a prime editor assess pathogenicity broad spectrum epithelial growth factor receptor gene (EGFR). Using pooled editing guide RNA libraries, install tens thousands spanning full coding sequence EGFR multiple cell lines role these tumorigenesis resistance tyrosine kinase inhibitors. Our scan identifies important hits, supporting robustness approach revealing underappreciated routes activation drug response. We anticipate that multimodal precision mutational can be applied broadly characterize variation any element interest at single-nucleotide resolution.

Language: Английский

Citations

8
The storm of NGS in NSCLC diagnostic-therapeutic pathway: How to sun the real clinical practice DOI Creative Commons
Giovanna De Maglio, Giulia Pasello, Mariella Dono

et al.

Critical Reviews in Oncology/Hematology, Journal Year: 2021, Volume and Issue: 169, P. 103561 - 103561

Published: Nov. 29, 2021

The increasing number of approved drugs along with next generation sequencing (NGS) technologies look out as potential revolution biomolecular characterization non-small-cell lung cancer (NSCLC). Nevertheless, several aspects impact on success rate NGS in clinical practice: a multidisciplinary approach and thorough knowledge strengths limits each technologic diagnostic tool are required. Crucial preliminary step is the selection best available sample before testing, aware condition setting disease. Genomic data should be than integrated context matched therapeutic options; Molecular Tumor Boards (MTB) worldwide emerging interdisciplinary groups implemented to transfer precision medicine practice. In order guarantee equity treatment, these considerations find their application widely rapidly. Aim this review offering an overview biomarkers, relative upcoming targeted drugs, new chances authors' perspective about real-life diagnostic-therapeutic algorithm useful for daily

Language: Английский

Citations

34
Cardiotoxicity Induced by Protein Kinase Inhibitors in Patients with Cancer DOI Open Access
Aleksandra Grela-Wojewoda, Renata Pacholczak‐Madej, Agnieszka Adamczyk

et al.

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(5), P. 2815 - 2815

Published: March 4, 2022

Kinase inhibitors (KIs) represent a growing class of drugs directed at various protein kinases and used in the treatment both solid tumors hematologic malignancies. It is heterogeneous group compounds that are widely applied not only different types but also positive for specific predictive factor. This review summarizes common cardiotoxic effects KIs, including hypertension, arrhythmias with bradycardia QTc prolongation, cardiomyopathy can lead to heart failure, as well less such fluid retention, ischemic disease, elevated risk thromboembolic events. The guidelines cardiac monitoring management most KIs discussed. Potential signaling pathways affected by likely contributing damage described. Finally, need further research into molecular mechanisms underlying cardiovascular toxicity these indicated.

Language: Английский

Citations

25
A narrative review of the role of common EGFR mutations in pathogenesis and treatment of non-small-cell lung carcinoma DOI Creative Commons
Mansi Sharma, Dharmishtha Basu, Shrinidhi Nathany

et al.

Cancer Research Statistics and Treatment, Journal Year: 2022, Volume and Issue: 5(3), P. 507 - 518

Published: July 1, 2022

ABSTRACT Epidermal growth factor receptor (EGFR) mutant non-small-cell lung cancer (NSCLC) is an important subtype of cancer. With the existing and ongoing research multiple targeted therapeutic options available, treatment landscape this subset rapidly evolving. This first review article in series on EGFR -mutant NSCLC which we describe structure , molecular biology common mutations, diagnostic modalities, various for all stages harboring mutations. We searched articles databases including OncoKB, NCBI: PubMed, Embase, Scopus, MyCancerGenome, using keywords “ ”, “NSCLC”, “Osimertinib”, “Gefitinib”. To compile review, a total 132 were utilized.

Language: Английский

Citations

23
Design, synthesis, and docking of novel thiazolidine‐2,4‐dione multitarget scaffold as new approach for cancer treatment DOI

Noura S. Hanafy,

Nada A. A. M. Aziz,

Sanadelaslam S. A. El‐Hddad

et al.

Archiv der Pharmazie, Journal Year: 2023, Volume and Issue: 356(7)

Published: May 5, 2023

Abstract Novel thiazolidine‐2,4‐diones have been developed and estimated as conjoint inhibitors of EGFR T790M VEGFR‐2 against HCT‐116, MCF‐7, A549, HepG2 cells. Compounds 6a, 6b , 6c were known to be the dominant advantageous congeners HCT116 (IC 50 = 15.22, 8.65, 8.80 µM), A549 7.10, 6.55, 8.11 MCF‐7 14.56, 6.65, 7.09 µM) 11.90, 5.35, 5.60 mass cell lines, correspondingly. Although compounds disclosed poorer effects than sorafenib 4.00, 4.04, 5.58, 5.05 tested sets, demonstrated higher actions erlotinib 7.73, 5.49, 8.20, 13.91 HCT116, cells, yet lesser performance on The hugely effective derivatives 4e–i 6a–c inspected versus VERO normal strains. 6b, 6c, 6a 4i found most derivatives, which suppressed by IC 0.85, 0.90, 1.50, 1.80 µM, respectively. Moreover, 6i could interfere with performing strongest 0.30, 0.35, 0.50, 1.00 What is more, represented satisfactory in silico computed ADMET profile.

Language: Английский

Citations

15
Pirfenidone Sensitizes NCI-H460 Non-Small Cell Lung Cancer Cells to Paclitaxel and to a Combination of Paclitaxel with Carboplatin DOI Open Access
Helena Branco, Júlio Oliveira, Catarina Antunes

et al.

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(7), P. 3631 - 3631

Published: March 26, 2022

Pirfenidone, an antifibrotic drug, has antitumor potential against different types of cancers. Our work explored whether pirfenidone sensitizes non-small cell lung cancer (NSCLC) lines to chemotherapeutic treatments. The cytotoxic effect paclitaxel in combination with three NSCLC (A549, NCI-H322 and NCI-H460) was evaluated using the sulforhodamine B assay. effects this on viability (trypan blue exclusion assay), proliferation (BrdU incorporation cycle (flow cytometry following PI staining) death (Annexin V-FITC detection assay Western blot) were analyzed most sensitive line (NCI-H460). drug also two non-tumorigenic (MCF-10A MCF-12A). Finally, ability sensitize NCI-H460 cells a plus carboplatin assessed. results demonstrated that sensitized treatment, reducing growth, proliferation, inducing alterations profile causing increase % death. Remarkably, did not cytotoxicity cells. Importantly, carboplatin. This highlights possibility repurposing chemotherapy for treatment NSCLC.

Language: Английский

Citations

20
cRGD-targeted gold-based nanoparticles overcome EGFR-TKI resistance of NSCLC via low-temperature photothermal therapy combined with sonodynamic therapy DOI
Wenhao Lv, Hao Wu, Yao Zhang

et al.

Biomaterials Science, Journal Year: 2023, Volume and Issue: 11(5), P. 1677 - 1691

Published: Jan. 1, 2023

Epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) is a first-line targeted drug for the treatment of advanced non-small cell lung cancer (NSCLC) in clinical practice, but EGFR-TKI-acquired resistance limits its therapeutic effect. To address this challenge, novel multifunctional gold-based nanoparticle-based delivery system fabricated. The nanoparticle loaded with EGFR-TKI (gefitinib) and IR780, surface-modified gold nanoshell layer has photothermal effect thermally triggered release. Finally, unique binding cyclic arginine-glycine-aspartic acid (cRGD) to αvβ3 ensured that (cRGD-GIPG) transport into drug-resistant NSCLC cells was functional. Due sonodynamic properties ultrasound (US) irradiation promoted reactive oxygen species (ROS) generation, while low-temperature therapy (PTT) not only release drug, also further enhanced cytotoxic effects ROS. In turn, it blocked activation TGF-β/PDLIM5/SMAD pathway induced apoptosis through mitochondrial apoptosis, enabling EGFR-TKI-resistant NSCLC. PTT combined (SDT) by cRGD-GIPG thus shows potent anticancer activity against vitro vivo. present work provides valuable strategy highly reversal

Language: Английский

Citations

13
A multiplex, prime editing framework for identifying drug resistance variants at scale DOI Creative Commons
Florence M. Chardon, Chase C. Suiter, Riza M. Daza

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: July 30, 2023

Abstract CRISPR-based genome editing has revolutionized functional genomics, enabling screens in which thousands of perturbations either gene expression or primary sequence can be competitively assayed single experiments. However, for libraries specific mutations, a challenge screening methods such as saturation is that only one region ( e.g. exon) studied per experiment. Here we describe prime-SGE (“prime editing”), new framework based on prime editing, mutations installed into genes throughout the and functionally assessed single, multiplex Prime-SGE quantifying abundance guide RNAs (pegRNAs) context selection, rather than themselves. We apply to assay nucleotide changes eight oncogenes their ability confer drug resistance three EGFR tyrosine kinase inhibitors. Although currently restricted positive selection by limited efficiency our strategy opens door possibility assaying vast numbers precise at locations genome.

Language: Английский

Citations

11