肿瘤相关碳酸酐酶是否真正适用于光动力疗法作为治疗靶点?
Are tumor-associated carbonic anhydrases genuine therapeutic targets for photodynamic therapy?
发表日期:2023 Sep 05
作者:
Amina Merabti, Sébastien Richeter, Claudiu T Supuran, Sébastien Clement, Jean-Yves Winum
来源:
EXPERT OPINION ON THERAPEUTIC TARGETS
摘要:
光动力疗法(PDT)是一种依赖于反应性氧化物种(ROS)的治疗方式,已成为一种替代癌症治疗策略。然而,在实体肿瘤中,PDT的治疗效果通常受到缺氧的严重限制,而这是许多肿瘤的典型特征。肿瘤相关的碳酸酐酶IX(hCA IX)和XII(hCA XII)在缺氧条件下表达增加,是实体肿瘤中具有吸引力并经过验证的抗癌药物靶点。目前,有效的PDT系统在治疗设计中面临的挑战是通过开发结合光敏剂和hCA IX/XII抑制剂的协同CA靶向治疗来克服缺氧的限制。本综述总结了有关使用hCA IX/XII抑制剂(CAi)靶向光敏化学系统用于对抗缺氧实体肿瘤的文献资料,以及最近的进展、挑战和未来前景。最近,以hCA IX/XII为重点的光敏化剂提供了具有相当潜力的新一代化合物。体内疗效研究的概念证明表明,CAi-PDT混合系统具有增强的疗效。进一步的研究需要加深我们对hCA IX/hCA XII抑制如何增强PDT以及获得更有效的相关衍生物的理解。
Photodynamic therapy (PDT) is a reactive oxygen species (ROS)-dependent treatment modality which has emerged as an alternative cancer therapy strategy. However, in solid tumors, the therapeutic efficacy of PDT is strongly reduced by hypoxia, a typical feature of many such tumors. The tumor-associated carbonic anhydrases IX (hCA IX) and XII (hCA XII), which are overexpressed under hypoxia are attractive, validated anticancer drug targets in solid tumors. Current challenges in therapeutic design of effective PDT systems aim to overcome the limitation of hypoxia by developing synergistic CA-targeted therapies combining photosensitizers and hCA IX/XII inhibitors.In this review, the current literature on the use of hCA IX/XII inhibitors (CAi) for targeting photosensitizing chemical systems useful for PDT against hypoxic solid tumors is summarized, along with recent progress, challenges, and future prospects.hCA IX/XII-focused photosensitizers have recently provided new generation of compounds of considerable potential. Proof of concept of in vivo efficacy studies suggested enhanced efficacy for CAi-PDT hybrid systems. Further research is needed to deepen our understanding of how hCA IX/hCA XII inhibition can enhance PDT and for obtaining more effective such derivatives.