Marriott J Blake, Dredge Keith, Dalgleish Angus G
Division of Oncology, Department of Cellular & Molecular Medicine, St George's Hospital Medical School, Cranmer Terrace, London, UK.
Curr Drug Targets Immune Endocr Metabol Disord. 2003 Sep;3(3):181-6. doi: 10.2174/1568008033340207.
Thalidomide is known to be effective in the treatment of a number of conditions, including leprosy and various cancers. The exact mechanisms of action remain unclear although these are known to include anti-tumour necrosis factor (TNF)-alpha, T cell costimulatory, anti-angiogenic and anti-tumour activities. However, thalidomide is being superceded by novel structural derivatives which have been designed to have improved immunomodulatory activity and side effect profiles. These are currently being characterised and some are entering the clinic in phase I/II studies. One novel group of structural analogues are classified as the Immunomodulatory Drugs (IMiDs). This review describes the emerging immunological, anti-angiogenic and direct anti-tumour properties of thalidomide and the characterisation and clinical application of its IMiD analogues. We describe the laboratory studies which have led to the characterisation and development of IMiDs into potentially clinically relevant drugs. Early trial data suggests that these compounds may themselves become established therapies, particularly in certain cancers. Furthermore, ongoing studies will determine how best to apply these compounds to the appropriate clinical settings. We will describe the various clinical studies of lead compounds that are in progress and speculate as to the potential and future development of these exciting compounds.
沙利度胺已知对多种病症有效，包括麻风病和各种癌症。尽管已知其作用机制包括抗肿瘤坏死因子（TNF）-α、T细胞共刺激、抗血管生成和抗肿瘤活性，但其确切作用机制仍不清楚。然而，沙利度胺正被新型结构衍生物所取代，这些衍生物被设计用于具有改善的免疫调节活性和副作用特征。目前正在对它们进行表征，一些正在进入I/II期临床研究。一类新型结构类似物被归类为免疫调节药物（IMiDs）。本综述描述了沙利度胺新出现的免疫学、抗血管生成和直接抗肿瘤特性及其IMiD类似物的表征和临床应用。我们描述了导致IMiDs表征和开发成为潜在临床相关药物的实验室研究。早期试验数据表明，这些化合物本身可能会成为既定疗法，特别是在某些癌症中。此外，正在进行的研究将确定如何最好地将这些化合物应用于适当的临床环境。我们将描述正在进行的先导化合物的各种临床研究，并推测这些令人兴奋的化合物的潜力和未来发展。
