Fig. 1

Mechanism of action and potential resistance mechanisms of HER2-targeted therapy: A HER2-targeted ADCs enter cells through endocytosis and release toxins that act on microtubules, DNA, or other materials, thereby inhibiting cell growth, proliferation, survival and metastasis. B HER2-targeted antibodies inhibit downstream signaling by binding to the extracellular domain of HER2 and preventing the formation of dimers between HER2 and other EGFR family members, in addition to releasing perforins and granzymes to act on target cells through ADCC. C TKIs inhibit signal transduction by binding to the intracellular tyrosine kinase domain of HER2. D HER2 heterogeneity, loss of HER2-positivity, mutation/amplification, alterations in intracellular signaling, protein overexpression, miRNAs, and abnormalities in either component of the ADC process can all lead to the development of drug resistance, which prevents cell death