Winum Jean-Yves, Scozzafava Andrea, Montero Jean-Louis, Supuran Claudiu T
Institut des Biomolécules Max Mousseron (IBMM) UMR 5247 CNRS-UM1-UM2 Bâtiment de Recherche Max Mousseron, Ecole Nationale Supérieure de Chimie de Montpellier, 8 Rue de l'Ecole Normale, 34296 Montpellier Cedex, France.
Anticancer Agents Med Chem. 2009 Jul;9(6):693-702. doi: 10.2174/187152009788680028.
Of the thirteen active carbonic anhydrase (CA) isozymes, the transmembrane isoform CA IX has been shown to be linked with carcinogenesis. CA IX presents an ectopic expression in a multitude of carcinomas derived from cervix, uteri, kidney, lung, oesophagus, breast, colon, etc., contrasting with its restricted expression in normal tissues, namely in the epithelia of the gastrointestinal tract. It has been demonstrated that this membrane-bound CA is strongly overexpressed in hypoxic tumors, participating in tumor cell environment acidosis and contributing to malignant progression and poor treatment outcome. Targeting CA IX could thus be an important means of controlling cancer disease. Modulation of extracellular tumor pH via inhibition of CA IX activity represents a promising approach to novel anticancer therapies. Much attention has recently been paid to the CA IX inhibitors drug design, and efforts have been made to obtain isozyme IX inhibitors, with putative applications as antitumor drugs/diagnostic agents. This review will focus on the different CA IX inhibitors described in the literature which could represent excellent potential as candidate therapeutic agents in cancer chemotherapy.
在13种活性碳酸酐酶（CA）同工酶中，跨膜同工型CA IX已被证明与致癌作用有关。CA IX在源自子宫颈、子宫、肾脏、肺、食道、乳腺、结肠等的多种癌症中呈异位表达，与其在正常组织（即胃肠道上皮）中的有限表达形成对比。已经证明，这种膜结合的CA在缺氧肿瘤中强烈过表达，参与肿瘤细胞环境酸中毒，并促进恶性进展和不良治疗结果。因此，靶向CA IX可能是控制癌症疾病的重要手段。通过抑制CA IX活性来调节细胞外肿瘤pH值是一种有前景的新型抗癌治疗方法。最近，人们对CA IX抑制剂的药物设计给予了极大关注，并努力获得同工酶IX抑制剂，有望将其用作抗肿瘤药物/诊断剂。本综述将聚焦于文献中描述的不同CA IX抑制剂，它们在癌症化疗中作为候选治疗药物具有巨大的潜力。
