BTK Degraders in Lymphoid Malignancies: New Modality, New Resistance Rules?

Abstract

After more than a decade of clinical experience with BTK inhibitors, resistance to BTK targeting has become a moving target, shaped by drug-specific BTK mutations, downstream signaling escape, and disease-dependent adaptive programs. The arrival of BTK degraders introduces a mechanistically distinct modality for lymphoid malignancies, but also raises a timely question: does degrading BTK rewrite the rules of resistance, or simply redraw its boundaries?