مقالات پذیرفته شده در هفتمین کنگره بین المللی زیست پزشکی
Investigating the Role of Gene Therapy in Breast Cancer
Investigating the Role of Gene Therapy in Breast Cancer
mahdieh balavar,1,*
1. BA student, Tehran, Azad University, Shahr Ray branch
Introduction: Breast cancer is the most common female malignancy in the United States. Breast cancer affects one in nine women in the United States. Yearly, 46,000 women die from breast cancer, despite early detection methods and advanced conventional treatments. Gene/prodrug systems can be used to selectively target malignant cancer cells while leaving normal cells unharmed. Thus, the application of these systems to reduce undesirable side effects has recently received increased attention. A gene therapeutic system using cytosine deaminase (CD)/5-fluorocytosine (5-FC). a gene-directed enzyme/prodrug therapy (GEPT) that currently exists, involves the conversion of a nontoxic drug (5-FC) into the toxic metabolite 5-fluorouracil (5-FU), an active anticancer drug that inhibits DNA synthesis in cancer cells. In addition, herpes simplex virus thymidine kinase (HSV-TK) suicide gene and its complementary prodrug ganciclovir (GCV) have been used to selectively target human types of cancers, indicating a potential therapeutic use of this gene delivery for primary human types of cancers. This GEPT system has been used to treat various types of cancer including colorectal and prostate cancer in clinical trials. In addition, CPT-11, which is hydrolyzed into a topoisomerase 1 inhibitor (SN-38) by carboxyl esterase (CE), has been administered to cancer patients, including ones with colorectal cancer for decades. Prodrugs appear to be associated with reduced toxicity in normal tissues but there are potential problems with exogenous enzyme delivery for selectively targeting tumor cells. The aim of this study was to investigate the Role of Gene Therapy In Breast Cancer.
Methods: This review study whit Investigating the role of gene therapy in breast cancer has written the from scientific databases such as Science Direct, Springer, Google Scholar, and PubMed.
Results: The wide range of delivery technologies now available have been explored in order to vehicle several classes of gene-based therapeutic agents. As distinct genetic alterations and gene expression profiles differentially affect the development and progression of breast cancer, correction of defective genes and regulation of gene expression through gene therapy has emerged as an innovative treatment strategy for breast cancer. Several approaches to induce genetic modification of a target cell have been evaluated, including transferring genes, segments of genes, or oligonucleotides such as siRNAs and miRNAs.The more classical view in gene therapy for cancer and other diseases was represented by the replacement of mutated genes with their normal counterparts. Indeed, loss-of-function mutations in tumor suppressor genes have been identified as key events in breast cancer, with subsequent uncontrolled tumor progression and onset of metastasis. Therefore, the transfection of cancer cells with completely functional tumor suppressor genes (e.g. TP53) has been investigated as an anticancer strategy with both viral vectors and few nanosystems, resulting in inhibition of breast tumor growth and apoptosis induction. Recent advancement in the genome editing systems has led to a significant increase of the efficiency and specificity of gene targeting using site-specific endonucleases, including ZFNs, TALENs, and CRIPR/Cas9. ZFPs and TALENs, which are composed of a customized DNA-binding module and a non-specific DNA cleavage domain, can generate multiple genetic modifications by inducing DNA double-strand breaks (DSBs) that stimulate the error-prone non-homologous end joining or the more specific homologous recombination pathways.
Conclusion: A variety of gene therapy approaches have been evaluated for treatment of breast carcinoma. The majority of clinical trials focus on the p53 TSG. The preferred way of administration is the intratumoral injection of an adenovirus p53 vector. Despite the observed higher transgene expression with the adenoviral vectors, clinical evidence of tumor regression occurred only in a small minority of patients. It is clear that gene therapy of breast cancer is a very difficult undertaking. The results of breast cancer gene therapy clinical trials to date have demonstrated little toxicity. However, the rate of clinical response has been low to date and efficient transgene expression remains to be challenge. In this regard, future research needs to focus not only on novel strategies and transgenes, but also on the development of novel gene transfer vectors to help overcome this inefficiency. The immediate future of breast cancer gene therapy would suggest increasing success in using cancer gene therapy as adjunct therapy in local control of many cancers.