Izzo Davide, Ascione Liliana, Guidi Lorenzo, Marsicano Renato Maria, Koukoutzeli Chrysanthi, Trapani Dario, Curigliano Giuseppe
Department of Oncology and Hemato-Oncology, University of Milan, Milan, Italy.
Division of New Drugs and Early Drug Development, European Institute of Oncology, IRCCS, Milan, Italy.
Ther Adv Med Oncol. 2025 Jan 2;17:17588359241309461. doi: 10.1177/17588359241309461. eCollection 2025.
Antibody-drug conjugates (ADCs) have emerged as a transformative approach in cancer therapy by enhancing tumor targeting and minimizing systemic toxicity compared to traditional chemotherapy. Initially developed with chemotherapy agents as payloads, ADCs have now incorporated alternative payloads, such as immune-stimulating agents, natural toxins, and radionuclides, to improve therapeutic efficacy and specificity. A significant advancement in ADC technology is the integration of Proteolysis Targeting Chimeras (PROTACs), which enable the precise degradation of cellular targets involved in tumorigenesis. This strategy enhances the specificity and precision of cancer therapies, addressing key mechanisms in cancer cell survival. Moreover, incorporating radioactive isotopes into ADCs is an emerging strategy aimed at further improving therapeutic outcomes. By delivering localized radiation, this approach offers the potential to enhance the efficacy of treatment and expand the therapeutic arsenal. Despite these innovations, challenges remain, including dysregulated immune activation, severe adverse effects, and intrinsic immunogenicity of some agents. These emerging issues highlight the ongoing need for optimization in ADC therapy. This review summarizes the latest developments in ADC technology, focusing on novel payloads, PROTAC integration, and the potential for combining ADCs with other therapeutic modalities to refine cancer treatment and improve patient outcomes.
抗体药物偶联物（ADCs）已成为癌症治疗中的一种变革性方法，与传统化疗相比，它能增强肿瘤靶向性并将全身毒性降至最低。最初，ADCs是以化疗药物作为有效载荷开发的，如今已纳入了其他有效载荷，如免疫刺激剂、天然毒素和放射性核素，以提高治疗效果和特异性。ADCs技术的一项重大进展是蛋白酶靶向嵌合体（PROTACs）的整合，它能够精确降解参与肿瘤发生的细胞靶点。这种策略提高了癌症治疗的特异性和精准性，针对癌细胞存活的关键机制发挥作用。此外，将放射性同位素纳入ADCs是一种旨在进一步改善治疗效果的新兴策略。通过提供局部辐射，这种方法有可能提高治疗效果并扩大治疗手段。尽管有这些创新，但挑战依然存在，包括免疫激活失调、严重不良反应以及某些药物的固有免疫原性。这些新出现的问题凸显了对ADCs疗法进行持续优化的必要性。本综述总结了ADCs技术的最新进展，重点关注新型有效载荷、PROTACs的整合以及将ADCs与其他治疗方式相结合以优化癌症治疗并改善患者预后的潜力。
