Mahon Brian P, Pinard Melissa A, McKenna Robert
Department of Biochemistry and Molecular Biology, College of Medicine, University of Florida, Gainesville, FL 32611, USA.
Molecules. 2015 Jan 30;20(2):2323-48. doi: 10.3390/molecules20022323.
Metastatic tumors are often hypoxic exhibiting a decrease in extracellular pH (~6.5) due to a metabolic transition described by the Warburg Effect. This shift in tumor cell metabolism alters the tumor milieu inducing tumor cell proliferation, angiogenesis, cell motility, invasiveness, and often resistance to common anti-cancer treatments; hence hindering treatment of aggressive cancers. As a result, tumors exhibiting this phenotype are directly associated with poor prognosis and decreased survival rates in cancer patients. A key component to this tumor microenvironment is carbonic anhydrase IX (CA IX). Knockdown of CA IX expression or inhibition of its activity has been shown to reduce primary tumor growth, tumor proliferation, and also decrease tumor resistance to conventional anti-cancer therapies. As such several approaches have been taken to target CA IX in tumors via small-molecule, anti-body, and RNAi delivery systems. Here we will review recent developments that have exploited these approaches and provide our thoughts for future directions of CA IX targeting for the treatment of cancer.
转移性肿瘤通常处于缺氧状态，由于瓦伯格效应所描述的代谢转变，其细胞外pH值会降低（约为6.5）。肿瘤细胞代谢的这种转变改变了肿瘤微环境，诱导肿瘤细胞增殖、血管生成、细胞运动、侵袭性，并且常常导致对常见抗癌治疗产生抗性；因此阻碍了侵袭性癌症的治疗。结果，表现出这种表型的肿瘤与癌症患者的预后不良和生存率降低直接相关。这种肿瘤微环境的一个关键成分是碳酸酐酶IX（CA IX）。已表明敲低CA IX表达或抑制其活性可减少原发性肿瘤生长、肿瘤增殖，并降低肿瘤对传统抗癌疗法的抗性。因此，已经采取了几种方法，通过小分子、抗体和RNAi递送系统来靶向肿瘤中的CA IX。在此，我们将综述利用这些方法的最新进展，并为未来靶向CA IX治疗癌症的方向提供我们的想法。
