Recent advances in the treatment of non-small cell lung cancer with MET inhibitors DOI Creative Commons
Dongna Zhang, Wenying Zhang, He Liu

et al.

Frontiers in Chemistry, Journal Year: 2024, Volume and Issue: 12

Published: Dec. 10, 2024

Recently, research into the oncogenic driver genes associated with non-small cell lung cancer (NSCLC) has advanced significantly, leading to development and clinical application of an increasing number approved therapeutic agents. Among these, small molecule inhibitors that target mesenchymal-epithelial transition (MET) have demonstrated successful in settings. Currently, three categories MET inhibitors, characterized by distinct binding patterns kinase region, been developed: types Ia/Ib, II, III. This review thoroughly examines MET’s structure its crucial role NSCLC initiation progression, explores discovery strategies for discusses advancements understanding resistance mechanisms. These insights are anticipated enhance a new generation high efficiency, selectivity, low toxicity, thereby offering additional alternatives patients diagnosed NSCLC.

Language: Английский

A Novel Digital PCR Assay for Accurate Detection and Differentiation of Focal and Non-Focal Subtypes of Mesenchymal–Epithelial Transition (MET) Gene Amplification in Lung Cancer DOI Open Access

Raymond C. M. Shek,

Peggy S. N. Li,

S. Leung

et al.

Cancers, Journal Year: 2025, Volume and Issue: 17(5), P. 811 - 811

Published: Feb. 26, 2025

Mesenchymal-epithelial transition (MET) gene amplification is a critical biomarker in non-small cell lung cancer (NSCLC), significantly influencing treatment decisions and prognostic evaluations. However, current detection methods such as fluorescence situ hybridization (FISH) next-generation sequencing (NGS) have limitations speed, cost, specificity, particularly when distinguishing between focal MET polysomy. This study introduces novel digital PCR (dPCR) assay designed not only to detect but also differentiate its non-focal subtypes. The was evaluated against established FISH targeted NGS panels using 55 NSCLC samples with known statuses (26 positive 29 negative) confirmed by NGS. Results dPCR demonstrated high sensitivity (96.0%) specificity (96.7%), achieving 100% concordance differentiating from Additionally, the exhibited excellent precision, accuracy, linearity (R2 = 1.00) copy number quantification, surpassing diagnostic performance. Offering robust, cost-effective, efficient alternative FISH, reduces turnaround time (3 h versus 2 days) provides quantitative objective method for subtype differentiation. makes it suitable clinical laboratories limited molecular expertise. highlights potential of complement existing techniques, delivering reliable actionable results MET-targeted therapy selection patients thereby advancing precision oncology.

Language: Английский

Citations

0
Decoding oncogenic secrets of regulator of chromosome condensation 1: A breakthrough mechanistic evidence from breast and lung cancer models DOI Creative Commons
Mohamed El‐Tanani, Shakta Mani Satyam, Syed Arman Rabbani

et al.

PLoS ONE, Journal Year: 2025, Volume and Issue: 20(3), P. e0319748 - e0319748

Published: March 31, 2025

The Regulator of Chromosome Condensation 1 (RCC1), a master regulator cell cycle progression, chromatin structure, and nuclear transport, emerges as powerful driver cancer progression. Elevated RCC1 expression in breast lung cancers is closely tied to enhanced tumor survival, proliferation, metastasis, positioning it promising therapeutic target. This study unveils RCC1’s pivotal role biology by silencing its MDA-MB-231 (breast cancer) A549 (lung lines using shRNA. knockdown dramatically reduced viability, colony formation, motility, while inducing apoptosis, evidenced increased apoptotic markers anti-apoptotic Bcl2 expression. Gene analysis revealed downregulation DNA repair pathways, highlighting critical sustaining oncogenic mechanisms. These findings underscore gatekeeper capable resisting apoptosis promoting metastasis. Targeting offers dual advantage: disrupting growth enhancing creating an exciting opportunity for precision therapies. By illuminating integration into survival networks, this not only advances our understanding but also lays the groundwork innovative treatments aimed at halting progression

Language: Английский

Citations

0
Genomic and Immune Landscape Comparison of MET Exon 14 Skipping and MET-Amplified Non-small Cell Lung Cancer DOI

Rachel L. Minne,

Natalie Y. Luo, Anne M. Traynor

et al.

Clinical Lung Cancer, Journal Year: 2024, Volume and Issue: 25(6), P. 567 - 576.e1

Published: Sept. 1, 2024

Language: Английский

Citations

2
Prominent response to savolitinib monotherapy in high-grade fetal adenocarcinoma with MET amplification and concurrent brain metastasis: a case report DOI Open Access
Lan Shen, Jikai Zhao, Yang Ying

et al.

Translational Lung Cancer Research, Journal Year: 2024, Volume and Issue: 13(6), P. 1407 - 1413

Published: June 1, 2024

Background: Mesenchymal-epithelial transition (MET) represents a potential therapeutic target in various cancers, with amplification of the MET gene identified subset patients pulmonary adenocarcinomas. However, is rarely observed high-grade fetal adenocarcinoma (H-FLAC). Case Description: Here we present novel case patient diagnosed stage IV H-FLAC harboring amplifications and treated savolitinib. The 69-year-old male patient, who presented primary complaint cough white sputum, had history hypertension for over 10 years 45-year smoking history. received savolitinib monotherapy treatment due to brain metastases. Despite omission radiotherapy asymptomatic metastases, notable response therapy was observed, partial (PR) achieved after 4 weeks reduction tumor. At time submission this report, 24 treatment, maintained PR. still undergoing treatment. This highlights clinical benefits targeted against H-FLAC. Conclusions: metastasis rare. Treatment resulted PR, providing preliminary insights efficacy amplification.

Language: Английский

Citations

0
Antibody–Drug Conjugates for the Treatment of Non-Small Cell Lung Cancer with Central Nervous System Metastases DOI Creative Commons

David J. H. Bian,

Sara Frida Cohen,

Anna-Maria Lazaratos

et al.

Current Oncology, Journal Year: 2024, Volume and Issue: 31(10), P. 6314 - 6342

Published: Oct. 18, 2024

Antibody-drug conjugates (ADCs) represent an emerging class of targeted anticancer agents that have demonstrated impressive efficacy in numerous cancer types. In non-small cell lung (NSCLC), ADCs become a component the treatment armamentarium for subset patients with metastatic disease. Emerging data suggest some exhibit activity even central nervous system (CNS) metastases, disease site is difficult to treat and associated poor prognosis. Herein, we describe summarize existing evidence surrounding NSCLC focus on CNS activity.

Language: Английский

Citations

0
Recent advances in the treatment of non-small cell lung cancer with MET inhibitors DOI Creative Commons
Dongna Zhang, Wenying Zhang, He Liu

et al.

Frontiers in Chemistry, Journal Year: 2024, Volume and Issue: 12

Published: Dec. 10, 2024

Recently, research into the oncogenic driver genes associated with non-small cell lung cancer (NSCLC) has advanced significantly, leading to development and clinical application of an increasing number approved therapeutic agents. Among these, small molecule inhibitors that target mesenchymal-epithelial transition (MET) have demonstrated successful in settings. Currently, three categories MET inhibitors, characterized by distinct binding patterns kinase region, been developed: types Ia/Ib, II, III. This review thoroughly examines MET’s structure its crucial role NSCLC initiation progression, explores discovery strategies for discusses advancements understanding resistance mechanisms. These insights are anticipated enhance a new generation high efficiency, selectivity, low toxicity, thereby offering additional alternatives patients diagnosed NSCLC.

Language: Английский

Citations

0