Gene therapy, an alternative efficient approach for cancer treatment
,1,* Rana najafi
,2 Zahra sadeghzadeh
,3 Sima ebrahim abadi
,4 Fatemeh radnia
,5 Touraj farazmand far
1. Golestan University of Medical Sciences , Gorgan , Iran
2. Golestan University of Medical Sciences , Gorgan , Iran
The cancer is one of the significant reasons for death in the world. up to now, many therapeutic approaches have been developed to deal with cancer which some of those are briefly described in this review. at the moment, the cancer treatment mainly contains surgery, chemotherapy, radiotherapy, and multimodality therapy. given that progress in cancer is still uncontrollable, attention to gene therapy has been increased. in gene therapy, viral and non-viral vectors are commonly used. in non-viral vectors, safety is an advantage and inefficiency is a defect. in contrast, for viral vector, efficiency is an advantage, and immunogenicity, pathogenesis and carcinogenesis are known as disadvantages.
one of the techniques used in gene therapy is the faulty gene modification. one of the mechanisms of gene modification is the replacement of the region with undesirable changes to the correct part, which can be performed by the homologous recombination. in this mechanism, the two molecules of dna are connected to each other through their homologous sequences, leading to the replacement of the genetic components. this regenerative mechanism is widely used in genetic engineering, especially gene editing. the displacement between non-homologous chromosomes (translocation) is one of the most common molecular mechanisms for the development of an acute lymphocytic leukemia cancer.
lentiviral vectors have improved the efficiency of gene transfer to non-divided cells. in the early stages of clinical testing, these safe and effective vectors have been used to transduction of autologous hematopoietic stem cells. oncolytic viruses are promising tools in cancer treatment. these viruses can specifically infect cancer cells and destroy them as well as alerting immune systems to attack cancer cells. when a virus infects the tumor cell, the virus replicates and make a plenty copies of itself until the tumor cell bursts. meanwhile, the dying cells release some materials like debris and tumor antigens that attract the immune system attention.
recently, the genome-editing technique has been developed that are based on engineered or bacterial nucleases. in contrast to viral vectors that can only act as a gene importer, genome editing methods provide a precision tool for adding, deleting and correcting the genes which are expected to be explored in the decade ahead. a bacteria immune system has recently been recognized as a crisper/cas9 system. in this system, the efficiency and accessibility of genome editing have been significantly improved. this bacterial immune system has been restored and has created a new revolution in the field of genome technology. recently, for the first time, the modified cells by crisper/cas9 have been used to treat human cancers.
the chimeric antigen receptor (car) engineered t cell technology was expanded as an adoptive cell therapy technique that was mhc-independent. the car receptor consists of three segments: 1-extracellular region usually containing an antibody-derived single-chain variable fragment (scfv). 2-transmembrane region. 3- the intracellular region contains the signal transduction domain of cd3z, and co-stimulatory molecules like cd28, 4-1bb, cd27 and ox40. in 2017, two car-t cell received fda approval, one for the treatment of children with all (acute lymphoblastic leukemia) and one for adult advanced lymphoma. but car-t cells for treating solid tumors, such as breast cancer and colorectal cancer, are not very effective for several reasons including:
1) specific tumor antigens are limit.
2) t-cells cannot effectively penetrate into the cancerous tissue.
3) if the car-t cells can penetrate the tumor, their function is lost by the tumor immunosuppressive microenvironment.
The newest cancer gene therapy methods that are expected to be effective and significant in the coming decades and accelerate the process of disease progression include homologous recombination, the use of viral and non-viral vector, car-t cells therapy and….
According to the methods described in this article, non-viral vectors are safer but less efficient than viral vectors. the homologous recombination method for the treatment of leukemias has been much considered by researchers, and car-t cell therapy has not been successful in treating solid tumors as leukemia.
The routine therapies in cancer treatment almost have a low efficiency and high side effects, the use of the above-mentioned methods may be a good alternative to cancer treatment in the future.
Cancer treatment, gene therapy, gene targeting, vectors, genome editing.