In CRC tumor models resistant to the EGFR MABs, tumor-generated high affinity EGFR ligands compete with PEPDG278D for EGFR binding, but aderbasib, an inhibitor of a disintegrin and metalloproteinase domain-containing protein 10 (ADAM10) and ADAM17 [23], inhibits EGFR ligand shedding from tumor cells and allows target engagement by PEPDG278D, resulting in significant inhibition of tumor growth, while aderbasib as a monotherapy is inactive. Here, EGFR is linked to neoplasm.