Scholarlink

<p>Non-small cell lung cancer (NSCLC) patients carrying HER2 exon 20 insertion (HER2 20ins) are respond poorly to conventional therapies and pan HER inhibitors. Trastuzumab Deruxtecan (T-DXd) has been approved in second line treatment in advanced NSCLC, but its efficacy in operable patients remains unclear. Here, we report a case of a patient with operable, HER2 20ins NSCLC who received neoadjuvant T-DXd, along with a second HER2 20ins patient who received conventional chemotherapy as a clinical reference. We utilized whole-genome sequencing (WGS) and immune microenvironment analysis to investigate the treatment’s impact. WGS analysis revealed marked reduction in tumor clones with genome instability and extrachromosomal DNA (ecDNA) following T-DXd treatment. Meanwhile, immune profiling demonstrated substantially increased CD8 + T cell infiltration in tumor cores with elevated PD-1 expression. In contrast, such changes in CD8 + T cell infiltration and PD-1 expression were not evident in another HER2 20ins patient who received conventional chemotherapy. These findings suggest that neoadjuvant T-DXd may represent a promising therapeutic option for locally advanced HER2-mutant NSCLC, warranting further investigation in larger cohorts.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Tumor genome and microenvironment alteration by trastuzumab deruxtecan as neoadjuvant therapy for HER2-mutant NSCLC

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年5月26日

查看全文
  • Jiangyang Li,
  • Xianfeng Lu,
  • Shuai Yue,
  • Ruyi Hang,
  • Xiaoyan Dai,
  • Xunjie Kuang,
  • Wei Guo,
  • Zhou Huang,
  • Yanli Xiong,
  • Mengxia Li

摘要

Non-small cell lung cancer (NSCLC) patients carrying HER2 exon 20 insertion (HER2 20ins) are respond poorly to conventional therapies and pan HER inhibitors. Trastuzumab Deruxtecan (T-DXd) has been approved in second line treatment in advanced NSCLC, but its efficacy in operable patients remains unclear. Here, we report a case of a patient with operable, HER2 20ins NSCLC who received neoadjuvant T-DXd, along with a second HER2 20ins patient who received conventional chemotherapy as a clinical reference. We utilized whole-genome sequencing (WGS) and immune microenvironment analysis to investigate the treatment’s impact. WGS analysis revealed marked reduction in tumor clones with genome instability and extrachromosomal DNA (ecDNA) following T-DXd treatment. Meanwhile, immune profiling demonstrated substantially increased CD8 + T cell infiltration in tumor cores with elevated PD-1 expression. In contrast, such changes in CD8 + T cell infiltration and PD-1 expression were not evident in another HER2 20ins patient who received conventional chemotherapy. These findings suggest that neoadjuvant T-DXd may represent a promising therapeutic option for locally advanced HER2-mutant NSCLC, warranting further investigation in larger cohorts.