Campsen Jeffrey, Zimmerman Michael A, Trotter James F, Wachs Michael, Bak Thomas, Mandell Susan, Kam Igal
University of Colorado Health Sciences Center, Division of Transplant Surgery, Denver, CO 80262, USA.
Expert Opin Pharmacother. 2007 Jun;8(9):1275-82. doi: 10.1517/14656566.8.9.1275.
Sirolimus (SRL) is a macrolide antibiotic that has potent antifungal and immunosuppressive properties; preclinical studies suggest that SRL may possess a significant antiproliferative influence in vitro. Recently, several studies have documented a negative effect by SRL on both primary tumor growth and the proliferation of metastatic foci in various rodent models of hepatocellular carcinoma (HCC). Orthotopic liver transplantation (OLT) is increasingly becoming a viable treatment option for patients with end stage liver disease and concomitant HCC. As such, an immunosuppressive agent with antineoplastic activity is inherently attractive in the setting of OLT for malignancy. Regrettably, the cumulative experience with SRL-based immunosuppression in this patient population is limited. Herein, the authors review the experience to date with SRL as a primary immunosuppressive agent following OLT, and discuss the clinical implications of SRL-based therapy in OLT recipients with cirrhosis and cancer.
西罗莫司（SRL）是一种具有强效抗真菌和免疫抑制特性的大环内酯类抗生素；临床前研究表明，SRL在体外可能具有显著的抗增殖作用。最近，多项研究记录了SRL对各种肝细胞癌（HCC）啮齿动物模型中的原发性肿瘤生长和转移灶增殖均有负面影响。原位肝移植（OLT）越来越成为终末期肝病合并HCC患者可行的治疗选择。因此，一种具有抗肿瘤活性的免疫抑制剂在OLT治疗恶性肿瘤时具有内在吸引力。遗憾的是，该患者群体中基于SRL免疫抑制的累积经验有限。在此，作者回顾了迄今为止将SRL作为OLT术后主要免疫抑制剂的经验，并讨论了基于SRL的治疗对OLT合并肝硬化和癌症受者的临床意义。
