文章：

抗逆转录病毒治疗的抗肿瘤作用

Antitumour effects of antiretroviral therapy

原文发布日期：2004-11-01

DOI: 10.1038/nrc1479

类型: Review Article

开放获取: 否

要点：

1. Infection with the human immunodeficincy virus (HIV) increases a patient's risk for developing certain types of cancers.
2. Immune hyperactivation, due to uncontrolled HIV replication, and immune deficiency have been shown to be the key factors in the initiation and progression of these cancers, particularly Kaposi's sarcoma and B-cell lymphomas, in HIV-infected patients.
3. Highly active antiretroviral therapy (HAART) reduces cancer risk and tumour burden in HIV-infected individuals.
4. The effects of these drugs cannot be entirely explained by their ability to suppress HIV replication and restore normal immune function — tumour development is not always correlated with a patient's viral load or level of immune reconstitution.
5. Direct antitumour effects of HAART could be related to specific actions of the protease inhibitors included in this therapeutic cocktail, such as ritonavir, saquinavir, indinavir and nelfinavir. These drugs have been shown to inhibit proliferation and induce apoptosis in cultured cancer cells, to block endothelial- and tumour-cell invasion, in vivo angiogenesis and tumour growth, as well as the inflammatory response.
6. The ability of these drugs to prevent tumour growth and progression might be mediated by their ability to inhibit proteasome function and the activity of matrix metalloproteinases.
7. As HAART has already been shown to be safe and effective for the treatment of patients with AIDS, these drugs might be exploited, alone or in combination with conventional cytotoxic therapy, for the treatment of non-HIV-infected patients with cancer.

要点翻译：

1. 人类免疫缺陷病毒（HIV）感染会增加患者罹患某些类型癌症的风险。
2. 研究表明，不受控制的HIV复制导致的免疫过度活化以及免疫缺陷是HIV感染者中这些癌症（特别是卡波西肉瘤和B细胞淋巴瘤）发生和发展的关键因素。
3. 高效抗逆转录病毒治疗（HAART）能够降低HIV感染者的癌症风险和肿瘤负荷。
4. 这些药物的效果不能完全用其抑制HIV复制和恢复正常免疫功能的能力来解释——肿瘤的发生并不总是与患者的病毒载量或免疫重建水平相关。
5. HAART的直接抗肿瘤作用可能与该治疗方案中包含的蛋白酶抑制剂（如利托那韦、沙奎那韦、茚地那韦和奈非那韦）的特定作用有关。研究表明，这些药物能够抑制培养癌细胞的增殖并诱导其凋亡，阻断内皮细胞和肿瘤细胞的侵袭、体内血管生成和肿瘤生长，以及炎症反应。
6. 这些药物预防肿瘤生长和进展的能力可能是通过抑制蛋白酶体功能和基质金属蛋白酶活性来介导的。
7. 由于HAART已被证明对艾滋病患者的治疗安全有效，这些药物或可单独使用，或与传统细胞毒性疗法联合，用于治疗非HIV感染的癌症患者。

英文摘要：

Infection by human immunodeficiency virus (HIV) is associated with an increased risk of certain tumours, particularly Kaposi's sarcoma, non-Hodgkin's lymphomas and cervical cancer. However, the incidence of these tumours in HIV-infected patients has decreased significantly since the widespread use of highly active antiretroviral therapy (HAART). This effect cannot be solely explained by the ability of these drugs to suppress HIV replication and thereby reconstitute the immune system. Recent studies have shown that inhibitors of the HIV aspartyl protease, which are widely used in HAART, have direct anti-angiogenic and antitumour effects that are unrelated to their antiviral activity. So these drugs might be used to treat cancer in patients who are not infected with HIV.

摘要翻译： 

人类免疫缺陷病毒（HIV）感染会增加某些肿瘤的风险，尤其是卡波西肉瘤、非霍奇金淋巴瘤和宫颈癌。然而，随着高效抗逆转录病毒治疗（HAART）的广泛应用，HIV感染者中这些肿瘤的发病率已显著下降。这一效应不能仅用这些药物抑制HIV复制从而重建免疫系统来解释。近期研究表明，HAART中广泛使用的HIV天冬氨酰蛋白酶抑制剂具有直接的抗血管生成和抗肿瘤作用，这些作用与其抗病毒活性无关。因此，这些药物可能被用于治疗未感染HIV的癌症患者。

原文链接：

Antitumour effects of antiretroviral therapy