Kapoor Anil
Department of Surgery, McMaster University, Hamilton, Ontario, Canada.
Drugs. 2008;68 Suppl 1:11-9. doi: 10.2165/00003495-200868001-00003.
Post-transplant malignancy morbidity and mortality are important limitations in kidney transplantation. The incidence of malignancy has been estimated at 20% after 10 years of chronic immunosuppression. The aetiology of post-transplant malignancy is multifactorial, with the increased risk for malignancy in transplant recipients correlating with overall exposure to immunosuppression. Strategies to understand and minimize the risk of developing malignancy in the transplant population are needed. Calcineurin inhibitors (CNIs) have been linked with post-transplant malignancies, while mammalian target of rapamycin (mTOR) inhibitors have shown antineoplastic activities. The dual efficacy of sirolimus as an immunosuppressive and antitumour agent has been demonstrated experimentally and clinically. Clinical studies have demonstrated a lower incidence of new malignancies after renal transplantation in recipients receiving immunosuppression with mTOR inhibitors compared with CNIs. Therapeutic protocols involving mTOR inhibitors may protect an allograft from immunological rejection, while at the same time addressing the problem of cancer in this high-risk population. Newer sirolimus analogues, such as temsirolimus, have become a focus in pure oncological research and are being evaluated for antineoplastic effects on a variety of malignancies in clinical trials.
移植后恶性肿瘤的发病率和死亡率是肾移植的重要限制因素。据估计，经过10年慢性免疫抑制后，恶性肿瘤的发病率为20%。移植后恶性肿瘤的病因是多因素的，移植受者发生恶性肿瘤的风险增加与免疫抑制的总体暴露相关。需要采取策略来了解并尽量降低移植人群发生恶性肿瘤的风险。钙调神经磷酸酶抑制剂（CNIs）与移植后恶性肿瘤有关，而雷帕霉素靶蛋白（mTOR）抑制剂已显示出抗肿瘤活性。西罗莫司作为免疫抑制剂和抗肿瘤药物的双重功效已在实验和临床中得到证实。临床研究表明，与接受CNIs免疫抑制的肾移植受者相比，接受mTOR抑制剂免疫抑制的受者移植后新发恶性肿瘤的发生率较低。涉及mTOR抑制剂的治疗方案可能保护同种异体移植物免受免疫排斥，同时解决这一高危人群中的癌症问题。新型西罗莫司类似物，如替西罗莫司，已成为纯肿瘤学研究的焦点，并正在临床试验中评估其对多种恶性肿瘤的抗肿瘤作用。
