摘要
Human epidermal growth factor receptor 2(HER2)overexpression and amplification activate key pathways driving tumor progression,leading to HER2-targeted therapies.However,HER2 signaling can also be aberrantly activated by somatic mutations,independent of overexpression or amplification,contributing to tumorigenesis[1].These mutations,found in domains such as the extracellular(ECD),transmembrane(TMD)/juxtamembrane(JMD),and tyrosine kinase(KD)regions,occur across cancers,from melanoma(1%)to bladder cancer(≤12%)[1,2],suggesting a significant population could benefit from HER2-targeted treatments.Neratinib,an irreversible pan-HER tyrosine kinase inhibitor,has shown efficacy in HER2-mutated cancers and is recommended in National Comprehensive Cancer Network guidelines[3].However,resistance mechanisms,such as secondary HER2 mutations or amplifications,may limit its efficacy[4,5],highlighting the need for combination therapies.
基金
supported by grants from the Korea Health Technology R&D Project through the Korea Health Industry Development Institute(KHIDI)
the Ministry of Health&Welfare,Republic of Korea(grant numbers:HI17C2206 and HA22C0012)
Additional support was provided by a grant from the National R&D Program for Cancer Control,National Cancer Center(NCC),Ministry of Health&Welfare,Republic of Korea(grant number:HA22C0052)
through the KOSMOS Molecular Tumor Board.
