A Cyclized Bivalent Aptamer-Based Protein Degrader Targeting Receptor Tyrosine Kinases Overcomes Resistance to Inhibitors in Lung Cancer

. In a preclinical NCI-H1975 tumor model pretreated with AHPC-cb-Ap, erlotinib achieved approximately 70% antitumor efficacy, comparable to that of the third-generation EGFR-TKI osimertinib. Taken together, our strategy of simultaneously degrading c-Met and EGFR, which underlie resistance to EGFR-TKIs, provides a comprehensive approach to combat the drug resistance of NSCLC.