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From gene therapy to virotherapy for ovarian cancer
M A Stoff-Khalili1, P Dall, D T Curiel
1Division of Human Gene Therapy, Gene Therapy Center, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
Abstract:
Ovarian cancer has the highest mortality of all cancers of the female reproductive system. Although progress in conventional therapies (surgery, chemotherapy and irradiation) has been achieved, the 5-year survival rate for patients with advanced stage ovarian cancer is still low. On this basis it is clear that there is a need for novel therapeutic paradigms. Targeted approaches are based on the increasing knowledge of the molecular basics of ovarian cancer. In this regard, gene therapy is a novel targeted approach for the treatment of ovarian cancer. However, current gene therapy delivery systems (viral and non-viral vectors) have to address the issues of inefficient transduction of target ovarian cancer cells and/or ectopic non-target delivery with attendant toxicity. Of note, the limited tumor transduction associated with current gene therapy interventions is due, in large part, to the fact that the employed vectors have been replication-incompetent. In this regard, human clinical trials have shown that the approach of replication-incompetent vectors has yet to succeed in ovarian cancer patients. In contrast, replication-competent viruses offer a method to achieve efficient tumor cell oncolysis (virotherapy) in ovarian cancer. Thus, in this very promising approach of virotherapy the replicating virus itself is the anti-cancer agent. This review discusses the concepts of gene therapy and virotherapy as novel targeted therapeutic approaches for the treatment of ovarian cancer.
Insights
Novel gene therapy and virotherapy offer new hope for ovarian cancer treatment. Replication-competent viruses show promise for efficient tumor cell destruction, overcoming limitations of current gene therapy delivery systems.
Area of Science:
- Oncology
- Gene Therapy
- Virotherapy
Background:
- Ovarian cancer has a high mortality rate, with low survival rates for advanced stages despite conventional treatments.
- Existing gene therapy approaches face challenges with inefficient delivery and toxicity.
- There is a critical need for innovative therapeutic strategies for ovarian cancer.
Purpose of the Study:
- To review gene therapy and virotherapy as novel targeted treatments for ovarian cancer.
- To highlight the limitations of current gene therapy delivery systems.
- To discuss the potential of replication-competent viruses in ovarian cancer treatment.
Main Methods:
- Review of existing literature on gene therapy and virotherapy for ovarian cancer.
- Analysis of challenges associated with viral and non-viral gene delivery vectors.
- Exploration of the concept of oncolysis using replication-competent viruses.
Main Results:
- Current gene therapy vectors often exhibit inefficient tumor transduction and potential off-target toxicity.
- Replication-incompetent vectors have shown limited success in clinical trials for ovarian cancer.
- Replication-competent viruses demonstrate potential for efficient tumor cell oncolysis.
Conclusions:
- Virotherapy, utilizing replicating viruses as anti-cancer agents, presents a promising avenue for ovarian cancer treatment.
- Targeted approaches like gene therapy and virotherapy are essential for improving patient outcomes.
- Further research into virotherapy is warranted to overcome existing therapeutic challenges in ovarian cancer.
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