胃癌（GC）是全球发生率第五高的恶性肿瘤，也是第四大导致癌症相关死亡的原因。尽管使用了多模式围手术化疗（pCT），但GC逐渐获得了化疗药物抗性，因此，鉴定适当的靶点以克服药物抗性是至关重要的。在潜在的生物标志物中，与多种实体肿瘤不良预后相关的碳酸酐酶IX（CAIX）引起了最多的关注。在接受围手术FLOT（即亚叶酸，5-氟尿嘧啶，多西他赛和奥沙利铂）或FOLFOX（即亚叶酸，5-氟尿嘧啶和奥沙利铂）的GC患者队列中，非反应组的肿瘤CAIX表达相对于反应组显示增加。此外，诱导对5-氟尿嘧啶，紫杉醇，顺铂或5-氟尿嘧啶，奥沙利铂和多西他赛组合产生抗性的GC细胞株相对于对照组过表达CAIX。相应地，高表达CAIX的GC细胞相比低表达细胞表现出更高的治疗抵抗性。值得注意的是，SLC0111显著改善了野生型和耐药型GC细胞的治疗反应。总体而言，这些数据表明CAIX与GC药物抗性之间存在关联，突出了SLC-0111在使GC细胞重新对pCT产生敏感性方面的潜力。版权所有 © 2023. Elsevier B.V.出版。

Gastric cancer (GC) is the fifth most frequent malignancy and the fourth leading cause of worldwide cancer-related death. Despite the usage of multimodal perioperative chemotherapy (pCT), GC progressively gains chemoresistance, thereby, the identification of suitable targets to overcome drug resistance is fundamental. Amongst the potential biomarkers, carbonic anhydrase IX (CAIX) - associated with a poor prognosis of several solid cancers - has gained the most attention. In a cohort of GC patients who received perioperative FLOT (i.e., Leucovorin, 5-Fluouracil, Docetaxel, and Oxaliplatin) or FOLFOX (i.e., Leucovorin, 5-Fluouracil, and Oxaliplatin), non-responder patients showed an increased expression of tumor CAIX compared to responder group. Moreover, GC cell lines induced to be resistant to 5-Fluouracil, Paclitaxel, Cisplatin, or the combination of 5-Fluorouracil, Oxaliplatin, and Docetaxel, overexpressed CAIX compared to the control. Accordingly, CAIX-high-expressing GC cells showed increased therapy resistance compared to low-expressing cells. Notably, SLC0111 significantly improved the therapy response of both wild-type and resistant GC cells. Overall, these data suggest a correlation between CAIX and GC drug resistance highlighting the potential of SLC-0111 in re-sensitizing GC cells to pCT.Copyright © 2023. Published by Elsevier B.V.