碳酸酐酶 (CA) 是一种金属酶，与需要调节组织 pH 值的多种病理生理过程有关。 CA IX 是缺氧诱导的肿瘤相关 CA 亚型，参与肿瘤细胞对酸中毒的适应。事实上，一些肿瘤驱动途径可以诱导 CA IX 表达，这反过来又与癌细胞侵袭和转移特征以及干细胞样特征、耐药性和复发的诱导有关。在其功能和结构表征之后，CA IX 靶向方法已被开发出来，以抑制其在肿瘤组织中的活性，迄今为止，该领域在治疗选择和生物学读数方面取得了令人难以置信的加速。小分子抑制剂、混合/双靶向药物、靶向抗体和过继性（基于 CAR-T 的）细胞疗法已在临床前水平开发，而磺酰胺 CA IX 抑制剂和抗体已进入治疗和成像的 Ib/II 期临床试验不同的实体瘤。本文将讨论 CA IX 在癌症生物学和药理学及其治疗靶向方面的最新进展。版权所有 © 2024。由 Elsevier B.V. 出版。

Carbonic anhydrases (CAs), are metallo-enzymes implicated in several pathophysiological processes where tissue pH regulation is required. CA IX is a tumor-associated CA isoform induced by hypoxia and involved in the adaptation of tumor cells to acidosis. Indeed, several tumor-driving pathways can induce CA IX expression, and this in turn has been associated to cancer cells invasion and metastatic features as well as to induction of stem-like features, drug resistance and recurrence. After its functional and structural characterization CA IX targeting approaches have been developed to inhibit its activity in neoplastic tissues, and to date this field has seen an incredible acceleration in terms of therapeutic options and biological readouts. Small molecules inhibitors, hybrid/dual targeting drugs, targeting antibodies and adoptive (CAR-T based) cell therapy have been developed at preclinical level, whereas a sulfonamide CA IX inhibitor and an antibody entered Phase Ib/II clinical trials for the treatment and imaging of different solid tumors. Here recent advances on CA IX biology and pharmacology in cancer, and its therapeutic targeting will be discussed.Copyright © 2024. Published by Elsevier B.V.