Mechanisms of resistance to antibody-drug conjugates in breast cancer

Antibody-drug conjugate (ADC) is a drug modality where a payload is conjugated to an antibody for its targeted delivery to the cancer cells. In breast cancer, the treatment landscape has changed remarkably in the past decade by the introduction of several effective ADCs in the clinic. However, intrinsic (de novo) or acquired resistance to these treatments is a major obstacle. In this review, we summarize the role of target antigen alterations, cell-intrinsic mechanisms that overcome payload cytotoxicity, and the pro-tumorigenic tumor microenvironment (TME) as the major drivers of resistance to ADCs. Furthermore, we discuss how different mechanisms of ADC resistance are integrated and highlight the most…

• FF
  Foundation for the National Institutes of Health

  Awards: R01CA267101, R01CA251374, R42CA275622