Non-small cell lung cancer as a target disease for herpes simplex type 1 thymidine kinase - ganciclovir gene therapy

Määttä, Ann-Marie; Tenhunen, Anni; Pasanen, Tiina; Meriläinen, Outi; Pellinen, Riikka; Mäkinen, Kimmo; Alhava, Esko; Wahlfors, Jarmo

doi:10.3892/ijo.24.4.943

Cited by 11 publications

(5 citation statements)

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“…Interestingly, histological investigations of surgical specimens, taken two to four weeks after the viral injection, showed apoptosis induction and decreased micro-vessel density [125]. Similarly, ample in vitro and in vivo studies show promising antineoplastic results with HSV-TK transduced tumor cells, i.e., cervical cancer cells [126] or lung cancer cells [127]. This strategy is in clinical trials with different types of cancer (Supplemental Data, Table S2).…”

Section: Ganciclovirmentioning

confidence: 91%

Repurposing of Antimicrobial Agents for Cancer Therapy: What Do We Know?

Pfab

Schnobrich

Eldnasoury

et al. 2021

Cancers

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The substantial costs of clinical trials, the lengthy timelines of new drug discovery and development, along the high attrition rates underscore the need for alternative strategies for finding quickly suitable therapeutics agents. Given that most approved drugs possess more than one target tightly linked to other diseases, it encourages promptly testing these drugs in patients. Over the past decades, this has led to considerable attention for drug repurposing, which relies on identifying new uses for approved or investigational drugs outside the scope of the original medical indication. The known safety of approved drugs minimizes the possibility of failure for adverse toxicology, making them attractive de-risked compounds for new applications with potentially lower overall development costs and shorter development timelines. This latter case is an exciting opportunity, specifically in oncology, due to increased resistance towards the current therapies. Indeed, a large body of evidence shows that a wealth of non-cancer drugs has beneficial effects against cancer. Interestingly, 335 drugs are currently being evaluated in different clinical trials for their potential activities against various cancers (Redo database). This review aims to provide an extensive discussion about the anti-cancer activities exerted by antimicrobial agents and presents information about their mechanism(s) of action and stage of development/evaluation.

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Section: Ganciclovirmentioning

confidence: 91%

Repurposing of Antimicrobial Agents for Cancer Therapy: What Do We Know?

Pfab

Schnobrich

Eldnasoury

et al. 2021

Cancers

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“…HSV-TK can catalyze GCV into monophosphorylated GCV (GCV-MP) that will then be converted into toxic gancyclovir triphosphate (GCV-TP) by other cellular kinases and thereafter cause cell growth inhibition or initiates cell death. According to previous studies NSCLC is a good target for HSV-TK gene therapy [ 6 ].…”

Section: Introductionmentioning

confidence: 99%

Potent anti-tumor activity of telomerase-dependent and HSV-TK armed oncolytic adenovirus for non-small cell lung cancer in vitro and in vivo

Zhang

Wei

Wang

et al. 2010

J Exp Clin Cancer Res

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BackgroundNon-small cell lung cancer (NSCLC) is the leading cause of cancer related mortality, any improvements in therapeutic strategies are urgently required. In this study we generated a novel 'suicide gene' armed oncolytic adenoviral vector and investigated its antitumor effect both in vitro and in vivo.MethodsSince the up-regulated expression of human telomerase reverse transcriptase (hTERT) is a hallmark of alltypes of NSCLC, we chose hTERT promoter to transcriptionally control E1A gene expression to obtain adenoviral replication in NSCLC. In order to further enhance anti-tumor effect of this oncolytic adenoviral vector, we inserted a 'suicide gene' i.e. Herpes Simplex Virus Thymidine Kinase (HSV-TK) into oncolytic adenoviral vector to engineer a novel armed oncolytic adenoviral vector 'Ad.hTERT-E1A-TK'.ResultsAd.hTERT-E1A-TK efficiently killed different types of tumor cells including two types of NSCLC cells in vitro, causing no damage to normal primary fibroblasts. Furthermore, Ad.hTERT-E1A-TK infection combined with administration of prodrug gancyclovir (GCV) resulted in more potent cytotoxicity on NSCLC cells, and synergistically suppressed human NSCLC tumor growth in nude mice.ConclusionThe results from this study showed that Ad.hTERT-E1A-TK/GCV could be a potent but safe anti-tumor strategy for NSCLC biotherapy.

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“…The effectiveness of suicide gene therapy using stem cells against various cancers, such as NSCLC, breast cancer, colon cancer, pancreatic cancer, and malignant melanoma, has been reported. 25 , 26 , 27 , 28 However, there are a few reports of suicide gene therapy using stem cells for brain metastasis. 29 , 30 , 31 Most of these reports are those using the cytosine deaminase (CD)/5-fluorocytosine (5-FC) system, and few use HSV-TK.…”

Section: Discussionmentioning

confidence: 99%

“… 32 Although typical human NSCLC cell lines are used in this study, it has been reported that the susceptibility to the HSV-TK/GCV system is different among the cell lines; adenocarcinoma and large-cell lung cancer are relatively sensitive to GCV. 26 Another advantage of the TK/GCV system using stem cells is that it only attacks tumor cells in contact with stem cells because metabolized GCV can spread to neighboring cells only through gap junctions. Therefore, the advantage of the TK/GCV system is that it is less harmful to normal tissues.…”

Section: Discussionmentioning

confidence: 99%