Challenges and Opportunities of Gene Therapy in Cancer

Abstract

Gene therapy involves either the direct introduction of genetic material (DNA or RNA) into the host cell (or organ), known as <em>in vivo</em> gene therapy, the re-introduction of the modified target cells taken out of the host, or <em>ex vivo</em> gene therapy. Cancer is mainly caused by the non-functioning of genes required for normal cell proliferation, and it has emerged as the leading cause of death globally due to the absence of efficient and safe therapies as well as early diagnostic modalities. Therapeutic trials using gene therapy have shown that they considerably increase the survival rate and life expectancy of patients with cancer. There are many potential strategies for the treatment of cancer using gene therapy currently being used, including (a) expressing a gene to induce apoptosis or increase tumor sensitivity to conventional drug/radiation therapy; (b) inserting a wild-type tumor suppressor gene to compensate for its loss/deregulation; (c) blocking the expression of an oncogene using an antisense (RNA/DNA) approach; and (d) enhancing tumor immunogenicity to stimulate immune cell reactivity. Gene therapy can employ many different genes, including anti-angiogenesis, any suicidal gene, immunotherapeutic gene, siRNA gene, pro-apoptotic gene, oncolytic gene, and gene-directed enzyme prodrug. Moreover, with advancements in gene transfer technologies, various kinds of new treatment strategies have been developed that complement conventional therapies used to treat cancer that are used to modify the DNA directly, such as zinc finger nucleases (ZFNs), transcription activator-like effector nucleases (TALENs), clustered regularly interspaced short palindromic repeats/CRISPR-associated protein 9 (CRISPR/Cas9), etc. Even though there has been a lot of progress in pre-clinical research in both better targeting and expression in a tumor-selective way, there are still a lot of problems that need to be fixed before it can be used in humans. These problems include non-specific expression, low-efficiency delivery, and biosafety. This review will highlight gene therapy's current challenges and future opportunities in cancer treatment.