Erb-B2 receptor tyrosine kinase 2 (HER2) exon 20 insertion mutant (HER2 exon 20 insertion)

Erb-B2 receptor tyrosine kinase 2 (HER2), encoded by the ERBB2 gene, is a member of the epidermal growth factor receptor (EGFR) family of receptor tyrosine kinases [1.1.1, 1.3.4]. Exon 20 insertion mutations in HER2 are oncogenic drivers that cause a conformational change in the kinase domain, leading to constitutive, ligand-independent activation [1.1.2, 1.4.2]. This activation stimulates downstream signaling through the PI3K-AKT and MEK-ERK pathways, promoting cell proliferation and survival [1.1.1, 1.2.2]. These mutations occur in approximately 1-4% of non-small cell lung cancers (NSCLC), predominantly in non-smokers and patients with adenocarcinoma [1.2.3, 1.3.4]. While traditional HER2-targeted therapies like trastuzumab have shown limited efficacy against these mutants, newer agents such as the antibody-drug conjugate trastuzumab deruxtecan and specialized tyrosine kinase inhibitors like poziotinib and pyrotinib have demonstrated significant clinical benefit [1.1.2, 1.3.1, 1.4.1]. Managing these patients requires careful monitoring for treatment-related toxicities, including interstitial lung disease and gastrointestinal issues [1.1.2, 1.3.3].

Other names

ERBB2 exon 20 insertionHER2 exon 20 mutationsHER2-YVMAHuman epidermal growth factor receptor 2 exon 20 insertionHER2 ex20ins

Irreversible inhibition of the ErbB receptor family tyrosine kinases and antibody-drug conjugate-mediated delivery of cytotoxic payloads.