Insights into the broad cellular effects of nelfinavir and the HIV protease inhibitors supporting their role in cancer treatment and prevention.
Insights into the broad cellular effects of nelfinavir and the HIV protease inhibitors supporting their role in cancer treatment and prevention.
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DOI：
10.1097/cco.0b013e328363dfee
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发表时间：
2013-09
影响因子：
3.4
通讯作者：
Ambinder RF
中科院分区：
文献类型：
--
作者：
Gantt S;Casper C;Ambinder RF
二十多年前，HIV蛋白酶抑制剂（PI）的发展预示着HIV护理的新时代，将感染从普遍致命变为慢性但可控。随着PI的广泛使用，HIV相关恶性肿瘤的发病率和死亡率降低。后来的研究发现这些药物具有很有希望的直接抗肿瘤作用。PI对几种细胞途径具有广泛的影响，这些途径对肿瘤发生很重要，并且不依赖于对HIV蛋白酶的抑制，包括减少血管生成和细胞侵袭、抑制Akt途径、诱导自噬和促进细胞凋亡。在PI中，奈非那韦似乎具有最有效和最广泛的抗肿瘤活性，并且还影响致癌疱疹病毒卡波西肉瘤相关疱疹病毒和EB病毒的复制。正在研究奈非那韦用于预防和治疗艾滋病毒感染者和非艾滋病毒感染者的各种恶性肿瘤。奈非那韦和其他PI是安全的口服药物，具有很好的抗肿瘤特性，可能在预防和治疗多种癌症中发挥重要作用。对PI作用机制的进一步了解可能会导致新型癌症化疗药物的开发。
The development of HIV protease inhibitors (PIs) more than two decades ago heralded a new era in HIV care, changing the infection from universally-fatal to chronic but controllable. With the widespread use of PIs, there was a reduction in the incidence and mortality of HIV-associated malignancies. Studies later found these drugs to have promising direct antitumor effects. PIs have a wide range of effects on several cellular pathways that are important for tumorigenesis and independent of inhibition of the HIV protease, including reducing angiogenesis and cell invasion, inhibition of the Akt pathway, induction of autophagy, and promotion of apoptosis. Among PIs, Nelfinavir appears to have the most potent and broad antineoplastic activities, and also affects replication of the oncogenic herpesviruses Kaposi sarcoma-associated herpesvirus and Epstein-Barr virus. Nelfinavir is being studied for the prevention and treatment of a wide range of malignancies in persons with and without HIV infection. Nelfinavir and other PIs are safe, oral drugs that have promising antitumor properties, and may prove to play an important role in the prevention and treatment of several cancers. Additional insights into PIs’ mechanisms of action may lead to the development of novel cancer chemotherapy agents.