سلول های بنیادی Mesenchymal: پلت فرم برای هدف قرار دادن ژن های انتحاری در سرطان Mesenchymal stem cells: A new platform for targeting suicide genes in cancer

Introduction Based on World Health Organization (WHO), Cancer is the second leading cause of death globally which was responsible for 8.8 million mortality in 2015. Nearly 1 in 6 deaths is due to cancer and the number of new cases is expected to rise by about 70% over the next 2 decades worldwide (Siegel et al., 2015; Torre et al., 2015). There are many types of cancer treatment including surgery, chemotherapy and radiotherapy (Amer, 2014). Cancerous patients had no survival benefits from current insufficient treatments and in most cases relapse and metastasis occurred (Nowakowski et al., 2016; Zhang et al., 2014). Such poor prognosis seems to be linked to: detrimental effects on vital noncancerous bodily tissues, deficient drug concentrations in tumors also problems of accessing tumor sites principally in metastatic cancers and systemic toxicity demonstrates the urgency to explore more effective anti-tumor therapy (Kim and Tannock, 2005; Liu et al., 2015; Pessino and Sobrero, 2006). Targeted therapy is emerging as a supplement or alternative to chemotherapy and/or radiation for various malignant diseases (Mirzaei et al., 2016c; Mirzaei et al., 2016g; Mirzaei et al., 2016j). In the field of targeted therapy, gene therapy appears as a good substitute method for cancer treatment(Wu et al., 2006). There are different approaches for cancer gene therapy including immunotherapy, oncolytic viruses and gene transfer (Cross and Burmester, 2006; Lin and Nemunaitis, 2004; McCormick, 2001; Mirzaei et al., 2016c; Mirzaei et al., 2016h). Immunotherapy employ for immune system stimulation to destroy cancer cells (Blattman and Greenberg, 2004). Oncolytic viruses, that replicates within the cancer cell and cause cell destruction (Chiocca and Rabkin, 2014; Dwyer et al., 2010; Singh et al., 2012). Gene transfer serves as a new treatment approach that introduces foreign genes into cancerous cells to promote cell death or slow the progression of the cancer. Gene transfer represents the best way for cancer gene therapy. In this path, we could introduce multiple genes with completely different function to malignant cell such as pro-apoptotic genes, anti-angiogenesis genes and suicide genes (Cao et al., 1998; Cross and Burmester, 2006; Persano et al., 2007). Failure to distinguish between normal and tumor cells will probably remain a limiting factor for chemotherapy drugs but Suicide genes form the basis of a strategy for making cancer cells more vulnerable and susceptible to chemotherapy (Karjoo et al., 2016b). Suicide gene therapy system is based on gene transfer into tumor cells, which leads to the exclusive expression of an enzyme able to convert a non-toxic prodrug into a lethal drug (Freeman, 2002; Izmirli et al., 2016; Touati et al., 2014).