High-throughput screened kaempferitrin potentiates trastuzumab efficacy in HER2-positive gastric cancer by targeting Cyclooxygenase-2 to inhibit ERK signaling - PubMed
3 days ago
- #HER2
- #Gastric Cancer
- #Kaempferitrin
- Kaempferitrin enhances trastuzumab efficacy in HER2-positive gastric cancer by targeting COX2 to inhibit ERK signaling.
- Trastuzumab resistance in HER2-positive gastric cancer is linked to MEK/ERK pathway hyperactivation.
- Kaempferitrin, derived from Traditional Chinese Medicine, was identified through high-throughput screening using an ERK-KTR reporter.
- Combination of trastuzumab and kaempferitrin inhibits proliferation and invasion of SNU-216 cells and reduces tumor growth and metastasis in mouse models.
- Kaempferitrin interacts with COX2 at Glu603, Thr198, and Gln440 to suppress ERK activation, sensitizing cancer cells to trastuzumab.
- A nano-delivery system (FKF) was developed for kaempferitrin, showing potent anti-tumor effects in patient-derived xenograft models.
- Toxicological evaluations confirm the combination therapy is well-tolerated.
- Kaempferitrin is a promising sensitizer for trastuzumab in HER2-positive gastric cancer therapy.