Cancer gene therapy

Tatjana Mitrovic,Sinisa Radulovic

doi:10.2298/aoo0501023m

Abstract

Cancer gene therapy can be defined as transfer of nucleic acids into tumor or normal cells with aim to eradicate or reduce tumor mass by direct killing of cells, immunomodulation or correction of genetic errors, and reversion of malignant status. Initially started with lots of optimism and enthusiasm, cancer gene therapy has shown limited success in treatment of patients. This review highlights current limitations and almost endless possibilities of cancer gene therapy. The major difficulty in advancing gene therapy technology from the bench to the clinical practice is problem with gene delivery vehicles (so called vectors) needed to ferry genetic material into a cell. Despite few reports of therapeutic responses in some patients, there is still no proof of clinical efficacy of most cancer gene therapy approaches, primarily due to very low transduction and expression efficacy in vivo of available vectors. An "ideal" gene therapy vector should be administrated through a noninvasive route and should be targeted not only to primary tumor mass but also to disseminated tumor cells and micrometastases; it should also carry therapeutic gene with tumor-restricted, time-regulated, and sustained expression. Current strategies for combating the cancer with gene therapy can be divided into four basic concepts: (1) replacement of missing tumor suppressor gene and/or blocking of oncogenes or pro-inflammatory genes, (2) suicide gene strategies, (3) induction of immune-mediated destruction, and (4) inhibition of tumor angiogenesis. The advance in the clinical benefit of gene therapy will probably be first achieved with combining it with standard cancer treatment: chemotherapy, radiotherapy, and immunotherapy.

Highlights

It is estimated that at least one in three will develop cancer and one in four men and one in five women will die from it [1]
There is no yet marketed cancer gene therapy, considerably progress has been made in defining strategies and targets for gene treatment of cancer
In spite selectivity and efficacy demonstrated in experimental systems and in clinical trials, cancer gene therapy still has few problems to solve before it becomes routinely adopted in clinic

Summary

Introduction

It is estimated that at least one in three will develop cancer and one in four men and one in five women will die from it [1]. Cancer gene therapy is based on utilization of safe viral delivery vehicles (vectors) for transfer therapeutic gene/s into cancer cells. Once transferred therapeutic gene(s) may has(have) various impacts: reparation or compensation of aberration-mutation or loss of genetic materials in cancer cells (for instance, correction of defective tumor suppressor gene - p53), killing tumor cells directly, amelioration of tumor antigen presentation on surface of tumor cells or stimulation of the immune response against a tumor, inhibition of tumor vasculature formation (antiangiogenesis), generation of marked population of cells for tracing the origins of recurrent tumors, protection of vulnerable cell population against treatments such as chemotherapy, or even enhancement of effect of conventional therapies (such as radiotherapy).

Results

Conclusion