Generating inhibitors for A Disintegrin And Metalloproteinase 10 (ADAM10), a zinc-dependent protease, was heavily invested in by the pharmaceutical industry starting over 20 years ago. There has been much enthusiasm in basic research for these inhibitors, with a multitude of studies generating significant data, yet the clinical trials have not replicated the same results. ADAM10 is ubiquitously expressed and cleaves many important substrates such as Notch, PD-L1, EGFR/HER ligands, ICOS-L, TACI, and the "stress related molecules" MIC-A, MIC-B and ULBPs. This review goes through the most recent pre-clinical data with inhibitors as well as clinical data supporting the use of ADAM10 inhibitor use in cancer and autoimmunity. It additionally addresses how ADAM10 inhibitor therapy can be improved and if inhibitor therapy can be paired with other drug treatments to maximize effectiveness in various disease states. Finally, it examines the ADAM10 substrates that are important to each disease state and if any of these substrates or ADAM10 itself is a potential biomarker for disease.

中文翻译：

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针对癌症和自身免疫中的 ADAM10。


解整合素和金属蛋白酶 10 (ADAM10) 是一种锌依赖性蛋白酶，制药行业从 20 多年前就开始大力投资生产解整合素和金属蛋白酶 10 (ADAM10) 抑制剂。人们对这些抑制剂的基础研究充满热情，大量研究产生了重要数据，但临床试验尚未复制相同的结果。 ADAM10 广泛表达，可裂解许多重要的底物，例如 Notch、PD-L1、EGFR/HER 配体、ICOS-L、TACI 以及“应激相关分子”MIC-A、MIC-B 和 ULBP。本综述回顾了抑制剂的最新临床前数据以及支持 ADAM10 抑制剂在癌症和自身免疫性疾病中使用的临床数据。它还讨论了如何改进 ADAM10 抑制剂治疗，以及抑制剂治疗是否可以与其他药物治疗结合使用，以最大限度地提高各种疾病状态的有效性。最后，它检查对每种疾病状态都很重要的 ADAM10 底物，以及这些底物或 ADAM10 本身是否是疾病的潜在生物标志物。