Davis Thomas W, Hunter Nancy, Trifan Ovidiu C, Milas Luka, Masferrer Jaime L
Pharmacia Corporation, St. Louis, Missouri, USA.
Am J Clin Oncol. 2003 Aug;26(4):S58-61. doi: 10.1097/01.COC.0000074158.59269.9F.
Prostaglandins have long been known to impact the radiosensitivity of cells and tissues, and many studies have centered on exploiting nonspecific prostaglandin inhibitors such as NSAIDs for therapeutic gain. These studies have ultimately been unsuccessful due to the lack of targeted specificity against the tumor. The discovery of the inducible cyclooxygenase enzyme (COX-2) and development of some highly selective inhibitors (which spare the constitutive COX-1 activity) has renewed excitement for modulating tumor prostaglandins as a method of specific radiosensitization of tumors, while sparing normal tissues. This review discusses these new data and generates a rationale for use of COX-2 inhibitors as radiosensitizing agents in cancer therapy.
长期以来,人们已知前列腺素会影响细胞和组织的放射敏感性,许多研究都集中在利用非特异性前列腺素抑制剂(如非甾体抗炎药)来获得治疗益处。由于缺乏针对肿瘤的靶向特异性,这些研究最终都没有成功。诱导型环氧化酶(COX-2)的发现以及一些高度选择性抑制剂(这些抑制剂可保留组成型COX-1活性)的开发,重新激发了人们将调节肿瘤前列腺素作为一种使肿瘤特异性放射增敏同时保护正常组织的方法的兴趣。本综述讨论了这些新数据,并提出了将COX-2抑制剂用作癌症治疗中放射增敏剂的理论依据。