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Abstract

Background: Oncolytic virotherapy has emerged as a novel and promising approach in cancer treatment, leveraging viruses that selectively infect and destroy malignant cells while sparing healthy tissues. Recent advancements in molecular biology and virology have enabled the development of genetically engineered viruses with enhanced tumor specificity, immune-stimulatory capacity, and safety profiles. As resistance to conventional therapies continues to pose a major clinical challenge, oncolytic viruses (OVs) offer a dual mechanism of action—direct tumor lysis and activation of antitumor immunity—placing them at the forefront of experimental oncology.
Objective: To analyze the challenges and future prospects associated with oncolytic virotherapy as a targeted cancer treatment strategy.
Methods: A systematic review was conducted using Google Scholar and PubMed databases. A total of 118 studies were initially identified. After applying inclusion and exclusion criteria, 28 full-text, peer-reviewed articles published between 2010 and 2025 were included. Data were extracted into structured tables summarizing study design, mechanisms of action, combination therapy strategies, challenges, and future directions of oncolytic virotherapy. A risk of bias assessment was also performed to evaluate study quality.
Results: Among the 28 studies reviewed, 60% were preclinical experimental models and 40% were clinical trials. Genetic engineering was reported to significantly enhance viral specificity, safety, and immune activation. Advanced delivery systems, including nanoparticles and cell carriers, showed improved targeting and persistence. However, major limitations included immune clearance, suppressive tumor microenvironments, and systemic delivery challenges. T-VEC remains the only FDA-approved OV, but newer candidates like CVA21 and BTV-10 show promise in early trials.
Conclusion: Oncolytic virotherapy represents a rapidly evolving cancer treatment modality with significant therapeutic potential. Overcoming delivery and immunological challenges through personalized and combination-based approaches may establish OVs as a core component of future oncology practice.