Adenoviral gene therapy in gastric cancer: A review

Table 1 A review of recent methods used in gastric cancer adenoviral gene therapy

Apoptosis inducers & tumor suppressors
Gene	Conclusion
FasL	Infection of human gastric carcinoma cells (SGC-7901) with Ad-FasL showed increased expression of FASL, resulting in apoptosis[32].
HDAC inhibitor	Induces apoptosis in cancer cells expressing wild and pseudo-wild type p53 via activating the p53 through acetylation[35].
E2F-1	E2F -1 is a transcription factor that regulates cell cycle progression into S-phase.
	Combining E2F-1 overexpression with cyclin-dependent kinase inhibitors results in an enhanced apoptotic response, causing nearly complete gastric tumor cell death[33].
Bax	In a study, Ad/Bax made marked Bax protein expression and effective apoptosis in MKN-1, MKN-7, MKN-28 gastric cell lines[34].
p51 and p53	p51 (p73L/p63/p40/KET), a p53 homologue, binds to p53-responsive elements to upregulate some p53 target genes and has been suggested to share partially overlapping functions with p53. p53 is an apoptosis promoting gene which could be used to eliminate tumor growth in gastric cancer. Adenovirally transduced p51A cDNA into human gastric cancer cells promotes apoptosis just like p53[36].
Caspase 8	Adv-Caspase 8 can selectively induce apoptosis in detached carcinoma cells[37].

Table 2 A review of recent methods used in gastric cancer adenoviral gene therapy

Metastasis inhibitors
Gene	Conclusion
NK4	Peritoneal tumors in mice treated early with adenoviral mediated NK4 were significantly reduced.
	In another study Ad.CMV.NK4 resulted in efficient production and secretion of NK4 and significantly inhibited proliferation, migration and invasion of gastric cancer cells[45].
Flt-1	When administered intra peritoneally it markedly reduced the number of metastatic nodules larger than 1 mm in diameter on the peritoneal surface[46].
Caspase 8	In a study it was determined that Caspase 8 can augment anoikis in MKN-45 cells and suppress its peritoneal dissemination in nude mice with xenograft gastric cancer transplants and consequently increase survival, Caspase 8 has also proved to be useful in limiting metastasis in other carcinomas originating from epithelial tissues[37].

Table 3 A review of recent methods used in gastric cancer adenoviral gene therapy

Targeted gene therapy
Method	Conclusion
HDAC inhibitor	Increase expression of the Coxackie adenovirus receptor and subsequent transfection efficiency of the adenovirus in cancer cells[35].
COX-2	COX-2 promoter shows the strongest cytocidal effect in gastric cancer cells when it is used in a conditionally replicating adenovirus (CRAD) context & with adenoviral vectors displaying 5/3 chimeric fibers[56].
EPCAM	It has been demonstrated that there is a marked difference in expression of the human epithelial cell adhesion molecule (EpCAM) between normal and (pre)malignant lesions of the stomach and esophagus. Based on this, using EpCAM to achieve gastric and esophageal adenocarcinoma selective gene transfer.may be a feasible choice for cancer-specific gene therapy[57].
	In a study using EPCAM antibody adhered to adenovirus, transduction of normal gastric epithelium and liver tissue was reduced at least 10-fold in comparison with native adenovirus however tumor transduction levels remained the same[58].
Carcinoembryonic antigen (CEA)	A remarkable degree of targeted gene delivery to gastric cancer cells was obtained with Adv-FZ33 with the fully human anti-carcinoembryonic antigen (CEA) monoclonal antibody, C2-45[59–62].