来那度胺在多发性骨髓瘤中的当前治疗用途。

Current therapeutic uses of lenalidomide in multiple myeloma.

作者信息

Hideshima Teru, Richardson Paul G, Anderson Kenneth C

机构信息

Jerome Lipper Multiple Myeloma Center, Dana-Farber Cancer Institute and Harvard Medical School, 44 Binney Street, Boston, MA 02115, USA.

出版信息

Expert Opin Investig Drugs. 2006 Feb;15(2):171-9. doi: 10.1517/13543784.15.2.171.

DOI:10.1517/13543784.15.2.171

PMID:16433596

Abstract

Thalidomide has demonstrated a broad spectrum of pharmacological and immunological effects, with potential therapeutic applications that span a wide spectrum of diseases: cancer and related conditions; infectious diseases; autoimmune diseases; dermatological diseases; and other disorders such as sarcoidosis, macular degeneration and diabetic retinopathy. Immunomodulatory derivative lenalidomide has more potent antitumour and anti-inflammatory effects. The molecular mechanisms of antitumour activity of lenalidomide have been extensively studied in multiple myeloma (MM). It directly induces growth arrest and/or apoptosis of even drug-resistant MM cells; inhibits binding of MM cells to bone marrow extracellular matrix proteins and stromal cells; modulates cytokine secretion and inhibits angiogenesis in the bone marrow milieu; and augments host antitumour immunity. Importantly, lenalidomide induces significant clinical responses even in patients with relapsed/refractory MM. Therefore, lenalidomide represents a new class of antitumour agents that is useful in the treatment of MM. Lenalidomide has received fast track designation from the FDA for the treatment of MM and myelodysplastic syndromes.

摘要

沙利度胺已展现出广泛的药理和免疫效应，其潜在治疗应用涵盖多种疾病：癌症及相关病症；传染病；自身免疫性疾病；皮肤病；以及其他病症，如结节病、黄斑变性和糖尿病性视网膜病变。免疫调节衍生物来那度胺具有更强的抗肿瘤和抗炎作用。来那度胺抗肿瘤活性的分子机制已在多发性骨髓瘤（MM）中得到广泛研究。它能直接诱导甚至耐药的MM细胞生长停滞和/或凋亡；抑制MM细胞与骨髓细胞外基质蛋白及基质细胞的结合；调节细胞因子分泌并抑制骨髓微环境中的血管生成；增强宿主抗肿瘤免疫力。重要的是，来那度胺即使在复发/难治性MM患者中也能诱导显著的临床反应。因此，来那度胺代表了一类新型抗肿瘤药物，可用于治疗MM。来那度胺已获得美国食品药品监督管理局（FDA）的快速通道认定，用于治疗MM和骨髓增生异常综合征。