Zarogoulidis Paul, Darwiche Kaid, Sakkas Antonios, Yarmus Lonny, Huang Haidong, Li Qiang, Freitag Lutz, Zarogoulidis Konstantinos, Malecki Marek
Pulmonary Department-Oncology Unit, "G. Papanikolaou" General Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece, EU ; Department of Interventional Pneumology, Ruhrlandklinik, West German Lung Center, University Hospital, University Duisburg-Essen, Essen, Germany, EU.
J Genet Syndr Gene Ther. 2013 Aug 9;4. doi: 10.4172/2157-7412.1000139.
Current cancer treatments may create profound iatrogenic outcomes. The adverse effects of these treatments still remain, as the serious problems that practicing physicians have to cope with in clinical practice. Although, non-specific cytotoxic agents constitute an effective treatment modality against cancer cells, they also tend to kill normal, quickly dividing cells. On the other hand, therapies targeting the genome of the tumors are both under investigation, and some others are already streamlined to clinical practice. Several approaches have been investigated in order to find a treatment targeting the cancer cells, while not affecting the normal cells. Suicide gene therapy is a therapeutic strategy, in which cell suicide inducing transgenes are introduced into cancer cells. The two major suicide gene therapeutic strategies currently pursued are: cytosine deaminase/5-fluorocytosine and the herpes simplex virus/ganciclovir. The novel strategies include silencing gene expression, expression of intracellular antibodies blocking cells' vital pathways, and transgenic expression of caspases and DNases. We analyze various elements of cancer cells' suicide inducing strategies including: targets, vectors, and mechanisms. These strategies have been extensively investigated in various types of cancers, while exploring multiple delivery routes including viruses, non-viral vectors, liposomes, nanoparticles, and stem cells. We discuss various stages of streamlining of the suicide gene therapy into clinical oncology as applied to different types of cancer. Moreover, suicide gene therapy is in the center of attention as a strategy preventing cancer from developing in patients participating in the clinical trials of regenerative medicine. In oncology, these clinical trials are aimed at regenerating, with the aid of stem cells, of the patients' organs damaged by pathologic and/or iatrogenic factors. However, the stem cells carry the risk of neoplasmic transformation. We discuss cell suicide inducing strategies aimed at preventing stem cell-originated cancerogenesis.
当前的癌症治疗可能会产生严重的医源性后果。这些治疗的副作用仍然存在，是执业医师在临床实践中必须应对的严重问题。尽管非特异性细胞毒性药物是对抗癌细胞的一种有效治疗方式，但它们也往往会杀死正常的快速分裂细胞。另一方面，针对肿瘤基因组的疗法正在研究中，其他一些疗法已经应用于临床实践。为了找到一种靶向癌细胞而不影响正常细胞的治疗方法，人们已经研究了几种方法。自杀基因疗法是一种治疗策略，其中将诱导细胞自杀的转基因导入癌细胞。目前主要采用的两种自杀基因治疗策略是：胞嘧啶脱氨酶/5-氟胞嘧啶和单纯疱疹病毒/更昔洛韦。新的策略包括沉默基因表达、表达阻断细胞重要途径的细胞内抗体以及半胱天冬酶和脱氧核糖核酸酶的转基因表达。我们分析了癌细胞自杀诱导策略的各种要素，包括：靶点、载体和机制。这些策略已经在各种类型的癌症中进行了广泛研究，同时探索了多种递送途径，包括病毒、非病毒载体、脂质体、纳米颗粒和干细胞。我们讨论了将自杀基因疗法应用于不同类型癌症的临床肿瘤学中的各个简化阶段。此外，自杀基因疗法作为一种防止参与再生医学临床试验的患者发生癌症的策略备受关注。在肿瘤学中，这些临床试验旨在借助干细胞使因病理和/或医源性因素受损的患者器官再生。然而，干细胞存在发生肿瘤转化的风险。我们讨论了旨在预防干细胞源性肿瘤发生的细胞自杀诱导策略。
