时间标签：数据日期 2026-10-31 · 生成时间 2026-11-01 05:30（Asia/Shanghai）｜ 检索窗口 PubMed edat 2026/10/28–2026/10/31 ｜ 情报发生日期 2026-10-31
研究问题
However, drug resistance limits the long-term efficacy of EGFR-TKIs [].；In addition to acquired resistance, primary resistance also remains an urgent clinical problem [].；Nevertheless, aggregating these recognized mechanisms, the driver remains unidentified in around 30–50% of patients in clinical practice, needing further investigation [, ].
方法
In this retrospective study, clinical data and samples were collected from 928 patients with NSCLC.；This cohort included 183 treatment-naïve baseline samples and 745 samples from patients with resistance to EGFR-TKIs.；The study was approved by the ethics committee of Shanghai East Hospital (K20-288).；Informed consent was obtained from all participants for genomic-level sequencing.
核心结论
These differences in sample type distribution between UR and baseline cohort was statistically significant (p = 0.0002).；In the overall, KR, and UR cohorts, plasma specimens showed significantly higher mean deduplicated sequencing depth than tissue specimens (all p < 0.05), while tissue specimens showed higher max VAF and mean VAF, reflecting higher tumor-cell content in solid biopsies rather than reduced detection sensitivity in plasma.；Moreover, 30.08% (154/512) of KR cohort harbored two or more concurrent resistance mechanisms. ‖ 结论：IKZF1 amplification emerged as a candidate, hypothesis-generating biomarker of primary resistance that requires validation in larger prospective cohorts and dedicated functional studies, which together may inform new therapeutic strategies for the approximately 30% of patients with unknown resistance.
局限
In contrast, patients with later-line resistance showed no significantly enriched differential genes, suggesting that tumors exposed to multiple lines of therapy display greater heterogeneity during evolution.；These findings suggest that PTPRD alterations may represent an overlooked novel target in EGFR-TKI resistance that warrants further exploration.；First of all, as a retrospective real-world study, our analysis is subject to potential selection bias, which may limit the generalization of the results.
对本项目的价值
★☆☆☆☆ 相关范围内，作为背景与横向对照收录。
全文来源
PMC JATS 全文（正文 32,741 字符，已过标题/DOI 逐字归属校验）
原文题录
- 英文标题：Genomic landscape of EGFR-TKI resistance: from known mechanisms to unknown resistance.
- 期刊与标识：Cell Oncol (Dordr) · PMID 42957912 · DOI 10.1007/s13402-026-01253-y
A 级证据分级：A 级（同行评议人体研究）
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