Scholarlink

<p><i>PIK3CA</i> mutation is frequently concurrent with known oncogenic drivers such as <i>EGFR</i> mutation in lung cancer, raising an interesting question about its real function. Cachexia is a systemic disease arising from tumor-organ crosstalk, significantly contributing to cancer-related mortality. Through integrative study of genetically engineered mouse models (GEMMs) and clinical data, we find concurrent <i>PIK3CA</i> mutant preferentially drives cachexia in <i>EGFR</i>-mutant lung cancer, promoting malignant progression instead of cancer initiation. <i>PIK3CA</i> mutant-mediated cachexia can be overcome by osimertinib (Osi) treatment in Osi-sensitive GEMM. In contrast, chemotherapy, routinely used in clinic for those relapsed from Osi therapy, fails to ameliorate cachexia in Osi-resistant GEMM despite notable tumor suppression. <i>PIK3CA</i> mutant-driven cachexia is mediated through NF-κB activation and can be dampened by combined aspirin treatment. This work provides insights into <i>PIK3CA</i> mutant biological function and mechanisms behind its clinical impacts, and proposes a potential strategy for clinical management.</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

Concurrent PIK3CA mutant promotes cachexia through inflammatory signaling in EGFR mutant lung cancer

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年12月16日

查看全文
  • Meiting Yue,
  • Zhen Qin,
  • Shijie Tang,
  • Xinlei Cai,
  • Yikai Zhao,
  • Chen Yang,
  • Liang Chen,
  • Luonan Chen,
  • Hongbin Ji

摘要

PIK3CA mutation is frequently concurrent with known oncogenic drivers such as EGFR mutation in lung cancer, raising an interesting question about its real function. Cachexia is a systemic disease arising from tumor-organ crosstalk, significantly contributing to cancer-related mortality. Through integrative study of genetically engineered mouse models (GEMMs) and clinical data, we find concurrent PIK3CA mutant preferentially drives cachexia in EGFR-mutant lung cancer, promoting malignant progression instead of cancer initiation. PIK3CA mutant-mediated cachexia can be overcome by osimertinib (Osi) treatment in Osi-sensitive GEMM. In contrast, chemotherapy, routinely used in clinic for those relapsed from Osi therapy, fails to ameliorate cachexia in Osi-resistant GEMM despite notable tumor suppression. PIK3CA mutant-driven cachexia is mediated through NF-κB activation and can be dampened by combined aspirin treatment. This work provides insights into PIK3CA mutant biological function and mechanisms behind its clinical impacts, and proposes a potential strategy for clinical management.