RE:Resistance to ADCs in the treatment of solid tumors "Since the first antibody–drug conjugate (ADC) was approved in 2000, the landscape of these targeted drugs has evolved over the years, profoundly changing the treatment scenario of various advanced-stage cancers, including solid tumors. With a better understanding of the construct’s mechanism of action and tumor biology, continuous efforts are made to fine-tune the ADC design and enhance the therapeutic index and tolerability of next-generation conjugates, promising to become the future of personalized cancer medicines. " - December 2023 Review
"This “Trojan horse” approach theoretically widens the therapeutic index of the cytotoxic agent by minimizing systemic drug exposure and dose-limiting toxicities to off-target healthy tissues, compared to standard chemo- and radiotherapies.
"The success of Enhertu® in low-HER2-expressing cancer patients underscores the high potential and complexities of this evolving class of drugs. While there remains a need to develop strategic means for matching each ADC construct with the most appropriate cancer type and patient population, the potential of future ADCs to address multiple cancer indications (using the right combination of I/O therapies) renews hope in this research area"
https://www.mdpi.com/2072-6694/16/2/447