Cancer is often driven by genetic mutations that cause abnormal protein expression and aberrant protein-protein interactions. The emerging field of chimeric drug molecules that link a target protein of interest to an effector protein capable of effectively destroying the target protein is currently revolutionizing oncology drug development. We present DEXTRACs as an innovative concept for targeted degradation of extracellular proteins.  This project aims to investigate whether DEXTRACs can efficiently mediate lysosomal degradation of disease-causing extracellular proteins, by combining synthetic chemistry, bioconjugation techniques, and protein engineering. Our objective is to gain a fundamental understanding of how to molecularly engineer DEXTRACs to maximize the avidity of ternary complex formation between the protein of interest and the lysosomal trafficking receptor on the cell surface. Moreover, we will evaluate the efficacy and selectivity of DEXTRACs for degrading proteins of interest in vitro and in vivo, in mouse tumor models.