| First Author | Yue M | Year | 2025 |
| Journal | Nat Commun | Volume | 17 |
| Issue | 1 | Pages | 704 |
| PubMed ID | 41398174 | Mgi Jnum | J:378407 |
| Mgi Id | MGI:8279566 | Doi | 10.1038/s41467-025-67345-9 |
| Citation | Yue M, et al. (2025) Concurrent PIK3CA mutant promotes cachexia through inflammatory signaling in EGFR mutant lung cancer. Nat Commun 17(1):704 |
| abstractText | 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-kappaB 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. |
