fig2

Figure 2. Mechanisms of resistance to ADCs. Resistance mechanisms include antigen loss or (1) decreased antigen binding, (2) impaired internalization, (3) inadequate intracellular trafficking leading to reduced payload release and (4) recycling of the ADC-antigen complex. Additional resistance pathways involve (5) upregulation of drug efflux transporters (e.g., MDR, Pgp), (6) lysosomal degradation defects, and (7) mutations in the payload target, all of which diminish ADC therapeutic efficacy. Created in BioRender. Larose, E. (2024) https://BioRender.com/f12z842. ADCs: Antibody-drug conjugates; MDR: multidrug resistance; Pgp: P-glycoprotein.