In situ gene therapy for prostate cancer.
In situ gene therapy for prostate cancer.
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DOI：
10.2174/1566523052997523
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发表时间：
2005-01
影响因子：
3.6
通讯作者：
T. Satoh;A. Irie;S. Egawa;S. Baba
中科院分区：
文献类型：
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作者：
T. Satoh;A. Irie;S. Egawa;S. Baba
在过去的十年中，前列腺癌的发病率在世界范围内急剧增加，许多国家的死亡率也在增加。一旦诊断出前列腺癌，重要的是迅速开始治疗方案，该方案可能治愈或阻止疾病进展。当疾病局限于前列腺时，可以通过根治性前列腺切除术或放射治疗治愈。然而，对于局部晚期、复发性或转移性疾病没有治愈性疗法。显然，这些患者需要新的治疗方法。基因治疗可能提供额外的治疗选择，有可能影响局部和转移性疾病。病毒介导的单纯疱疹病毒胸苷激酶（HSV-tk）基因转移的转导，随后是前药更昔洛韦（GCV）的过程，即所谓的自杀基因治疗，已经被一些研究者证明。目前的原位基因治疗人前列腺癌的临床试验证明了安全性、临床疗效和抗肿瘤活性的生物学效应。HSV-tk前列腺癌的临床试验也正在日本、荷兰和墨西哥进行。目前，许多临床前研究报道了免疫调节细胞因子基因治疗，如白细胞介素-2、白细胞介素-12、B7-1（CD 80）、B7-2（CD 86）和粒细胞-巨噬细胞集落刺激因子。几项临床研究已经获得批准，可能会表明这些免疫调节基因疗法可能产生有效的局部和全身抗肿瘤活性，并为前列腺癌患者提供选择。我们回顾了目前原位基因治疗（基因/免疫治疗）涉及的多个问题，其结果，以及前列腺癌患者的未来方向。
The incidence of prostate cancer has dramatically increased worldwide in the past decade, with mortality rates also increasing in many countries. Once prostate cancer is diagnosed, it is important to rapidly begin a treatment regimen that is either potentially curative or impedes disease progression. When the disease is confined to the prostate, it can be cured by radical prostatectomy or irradiation therapy. However, there are no curative therapies for locally advanced, recurrent, or metastatic diseases. Clearly, new therapies are needed for these patients. Gene therapy may provide additional therapeutic options with the potential to affect both localized and metastatic disease. Virus-mediated transduction of the herpes simplex virus thymidine kinase (HSV-tk) gene transfer, followed by a course of the prodrug ganciclovir (GCV), so-called suicide gene therapy, has been demonstrated by several investigators. The present in situ gene therapy clinical trial for human prostate cancer demonstrated safety, clinical efficacy, and biological effects of antitumor activity. HSV-tk clinical trials for prostate cancer are also ongoing in Japan, the Netherlands, and Mexico. Currently, numerous preclinical studies have reported immunomodulatory cytokine gene therapy, such as interleukin-2, interleukin-12, B7-1 (CD80), B7-2 (CD86) and granulocyte-macrophage colony-stimulating factor. Several clinical studies have been approved that potentially will show that these immunomodulatory gene therapies may generate an effective local and systemic antitumor activity and that should provide options for patients with prostate cancer. We review the multiple issues involved in current in situ gene therapy (gene/immunotherapy), its outcome, and future directions for patients with prostate cancer.