title: Suicide Gene Therapy for Cancer - Current Strategies.
abstract: 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.
authors.affiliation: 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.
authors.forename: Paul
authors.initials: P
authors.lastname: Zarogoulidis
authors.forename: Kaid
authors.initials: K
authors.lastname: Darwiche
authors.forename: Antonios
authors.initials: A
authors.lastname: Sakkas
authors.forename: Lonny
authors.initials: L
authors.lastname: Yarmus
authors.forename: Haidong
authors.initials: H
authors.lastname: Huang
authors.forename: Qiang
authors.initials: Q
authors.lastname: Li
authors.forename: Lutz
authors.initials: L
authors.lastname: Freitag
authors.forename: Konstantinos
authors.initials: K
authors.lastname: Zarogoulidis
authors.forename: Marek
authors.initials: M
authors.lastname: Malecki
keywords: Cancer; Non-viral vectors; Regenerative medicine; Suicide gene therapy; Transporters; Viral vectors