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Jie Lin

Publications and source records attributed to Jie Lin.

3 recordsLinked to original sources
PubMed2026

DESTINY-Lung06: trastuzumab deruxtecan and pembrolizumab as first-line treatment for HER2-overexpressing, PD-L1 TPS&#x2009;<50% NSCLC.

Non-small cell lung cancer (NSCLC) that overexpresses human epidermal growth factor receptor 2 (HER2) is associated with poor prognosis, and no HER2-targeting therapies for HER2-overexpressing NSCLC are currently approved in the first-line setting. Pembrolizumab plus pemetrexed and platinum-based chemotherapy is a recommended first-line treatment option for nonsquamous NSCLC with no actionable genomic alterations. However, improved outcomes with pembrolizumab-based therapies correlate with higher programmed death-ligand 1 (PD-L1) levels, underscoring the need for more targeted treatment options for patients with lower PD-L1 tumor proportion scores (TPS; <50%). DESTINY-Lung06 is a multicenter, open-label, randomized, phase III trial evaluating the efficacy and safety of trastuzumab deruxtecan (T-DXd) in combination with pembrolizumab in the first-line setting in patients with HER2-overexpressing (&#x2265;25% moderate/strong membrane staining), PD-L1 TPS&#x2009;<50% NSCLC. Planned enrollment will be approximately 686 patients randomly assigned to either T-DXd 5.4&#x2009;mg/kg with pembrolizumab 200&#x2009;mg intravenously every 3&#x2009;weeks (Q3W) or pembrolizumab 200&#x2009;mg plus pemetrexed 500&#x2009;mg/m2 with platinum-based chemotherapy (cisplatin 75&#x2009;mg/m2 or carboplatin under the concentration-time curve 5&#x2009;mg min/mL) intravenously Q3W. Progression-free survival by blinded independent central review and overall survival are the primary and key secondary endpoints of the study, respectively.Clinical trial registration: www.ClinicalTrials.gov identifier is NCT06899126; EudraCT identifier is 2024-515658-26-00.

First-line↗
PubMed2026

Comprehensive characterization of MET exon 14 skipping mutations in non-small cell lung cancer.

BACKGROUND: MET exon 14 skipping mutation (MET&#x394;ex14) is a key driver event in non-small cell lung cancer (NSCLC) and can emerge as an acquired drug resistance mechanism to MET, EGFR or ALK inhibitors. The clinical and genomic features of MET&#x394;ex14 in NSCLC require further characterization. METHODS: Our study included a total of 585 patients with MET&#x394;ex14&#x2009;+&#x2009;NSCLC, comprising 556 baseline samples, 53 samples from patients exhibiting resistance to MET inhibitors, and 16 samples from patients resistant to EGFR/ALK inhibitors. Genomic data from targeted next-generation sequencing (NGS) of tissue and/or plasma samples using GeneseeqPrime&#x2122; (a 425 pan-cancer gene panel) were analyzed. RESULTS: Overall, MET&#x394;ex14 exhibited a prevalence of 1.02% (n&#x2009;=&#x2009;585) in the screened NSCLC population, with a higher incidence in patients with a sarcomatoid histology. MET&#x394;ex14 was predominantly detected at the splice donor site, though the non-coding region adjacent to the splice acceptor site contributed considerably to the complexity of MET&#x394;ex14. Common concurrent alterations identified at baseline included those in TP53 (40.8%), CDK4 (16%) and EGFR (12.4%). Concurrent MET amplification and cell cycle pathway mutations were both associated with worse outcomes in patients treated with crizotinib, with significant co-occurrences observed also among these concurrent genomic variations. In addition, increased chromosomal instability and intra-tumoral heterogeneity correlated with a poorer response to crizotinib. Mechanisms of acquired resistance to MET inhibitors were primarily attributed to on-target MET D1228X/Y1230X mutations or off-target alterations within genes in the RTK/RAS/MAPK and PI3K/AKT/mTOR pathways. Intriguingly, our exploratory analysis also identified the FGFR3::TACC3 fusion as a potential resistance mechanism to savolitinib. Moreover, MET&#x394;ex14 was identified in 16 patients following progression on EGFR and ALK inhibitors, highlighting the need for developing tailored therapeutic strategies to overcome resistance. CONCLUSIONS: This study provides a comprehensive characterization of MET&#x394;ex14 in NSCLC, revealing its dual role as a primary driver of oncogenesis and a potential resistance mechanism to EGFR/ALK inhibitors. The identification of concurrent genetic alterations and potential resistance mechanisms enhances our molecular understanding of treatment responses. These findings highlight the need for further investigation into targeted therapies that consider the genomic complexity of MET&#x394;ex14 to improve treatment efficacy and patient outcomes.

Humans↗
PubMed2026

Genetic Variation and Evolutionary Characteristics of Coxsackievirus B1: F3 Subtype Associated With Hand, Foot and Mouth Disease in China.

Coxsackievirus B1 (CV-B1) is primarily associated with meningitis but can also cause localized outbreaks of hand, foot, and mouth disease (HFMD). This study analyzed the genetic diversity of the VP1 gene in 39 strains of the CVB1 virus isolated from HFMD children across 15 provinces in China between 2010 and 2024, as well as 179 strains from 17 countries. Based on the average nucleotide difference of VP1 gene, we classified CVB1 virus into six genotypes A to F, Notably, genotype F is newly classified. Since 2010, genotype F guadually replaced genotype E as the dominant genotype in China and has further subdivided into three subtypes: F1, F2, and F3, with F3 being the most prevalent subtype in China currently. We specifically study the mild and severe cases within the F3 subtype. Temperature-sensitivity experiments revealed no differences between mild and severe cases of the F3 subtype, and they all belong to temperature-sensitive strains. Interestingly, we found that mild cases of the F3 subtype did not involve recombination, whereas all severe cases of the F3 subtype showed recombination with Coxsackievirus B4 (CVB4). CVB4 has consistently been the primary pathogen responsible for severe neonatal illnesses, suggesting that recombination between the F3 subtype and CVB4 may be associated with the development of severe HFMD. These findings provide fundamental scientific data for further investigation into the epidemiology and genetic characteristics of variants of Coxsackievirus B1 in China.

Humans↗