Abstract:
Antibody-drug conjugates (ADCs) are an emerging class of anticancer agents that combine targeting antibodies with potent cytotoxic agents. Their molecular configuration allows for increased therapeutic efficacy and reduced adverse-effect profiles compared to monoclonal antibodies or cytotoxic chemotherapy alone. ADCs cause off-target toxicities through several mechanisms, including premature deconjugation of the cytotoxic agent in the serum and the presence of the targeted antigen on normal tissues. Given cutaneous adverse events comprise 31.3% of all-grade adverse events in clinical trials involving ADCs, dermatologists are increasingly called upon to manage the cutaneous toxicities caused by these drugs. In this review, we summarize known cutaneous toxicities of the ADCs that have been approved for use by the US Food and Drug Administration to date. Dermatologists can play a key role in recognizing cutaneous reactions associated with ADCs, contributing to guidelines for their management, and aiding during clinical trials to generate detailed morphologic and histopathologic descriptions of cutaneous toxicities caused by ADCs.
摘要:
抗体-药物缀合物是一类新兴的抗癌剂,其将靶向抗体与有效的细胞毒性剂组合。与单独的单克隆抗体或细胞毒性化疗相比,它们的分子构型允许增加的治疗功效和降低的不良反应谱。抗体-药物缀合物通过几种机制引起脱靶毒性,包括血清中细胞毒性剂的过早去偶联和正常组织上靶向抗原的存在。在涉及抗体-药物偶联物的临床试验中,皮肤不良事件占所有级别不良事件的31.3%,皮肤科医生越来越多地要求管理这些药物引起的皮肤毒性。在这次审查中,我们总结了迄今为止已被美国食品和药物管理局批准使用的抗体-药物偶联物的已知皮肤毒性.皮肤科医生可以在识别与抗体-药物缀合物相关的皮肤反应中发挥关键作用。为他们的管理提供指导,并在临床试验期间帮助生成由抗体-药物缀合物引起的皮肤毒性的详细形态学和组织病理学描述。