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Eukaryotic expression vectors bearing genes encoding cytotoxic proteins for cancer gene therapy
1Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow 117997, Russia. em_glinka@mail.ru
Abstract:
Cancer gene therapy is a promising direction for the treatment of cancer patients. A primary goal of all cancer therapies is to selectively target and kill tumour cells. Such therapies are administered via different approaches, including both viral and non-viral delivery; however, both methods have advantages and disadvantages. Transcriptional targeting enables genes encoding toxic proteins to be expressed directly in cancer cells. Numerous vectors have been created with the purpose of killing cancer cells, and some have successfully suppressed malignant tumours. Data concerning the function of vectors bearing genes that encode cytotoxic proteins under the control of different promoters, including tissue/tumour specific and constitutive promoters, is summarised here. This review focuses on vectors that bear genes encoding diphtheria toxin, Pseudomonas exotoxin A, caspases, gef, streptolysin, and melittin. Data describing the efficacy of such vectors have been summarised. Notably, there are vectors that killed cancer cell lines originating from the same type of cancer with differential efficiency. Thus, there is differential inhibition of cancer cell growth dependent on the cell line. In this review, the constructs employing genes whose expression induces cell death and the efficiency with which they suppress cancer cell growth will be summarised.
Insights
Cancer gene therapy utilizes vectors to deliver toxic genes specifically to tumor cells, offering a promising treatment approach. Different vectors show varying efficiencies in killing cancer cells, highlighting the need for tailored therapeutic strategies.
Area of Science:
- Oncology
- Molecular Biology
- Biotechnology
Background:
- Cancer gene therapy aims to selectively eliminate tumor cells.
- Viral and non-viral delivery systems are employed, each with limitations.
- Transcriptional targeting allows for cancer cell-specific expression of toxic genes.
Purpose of the Study:
- To review vectors designed for cancer gene therapy.
- To summarize data on vectors encoding cytotoxic proteins like diphtheria toxin and Pseudomonas exotoxin A.
- To analyze the efficacy of different promoters in driving toxic gene expression in cancer cells.
Main Methods:
- Review of existing literature on cancer gene therapy vectors.
- Analysis of data on vectors utilizing tissue/tumor-specific and constitutive promoters.
- Focus on vectors encoding diphtheria toxin, Pseudomonas exotoxin A, caspases, gef, streptolysin, and melittin.
Main Results:
- Various vectors have been developed to kill cancer cells, with some successfully suppressing tumors.
- Vectors exhibit differential efficiency in killing cancer cell lines, even within the same cancer type.
- The choice of promoter and cytotoxic gene influences the efficacy of cancer cell growth inhibition.
Conclusions:
- Cancer gene therapy holds significant promise for cancer treatment.
- Vector design, including promoter selection and cytotoxic payload, is critical for therapeutic success.
- Further research is needed to optimize vector efficiency and overcome cell-line-specific responses for improved cancer treatment outcomes.
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