Oncolytic viruses: advanced strategies in cancer therapy.

This review article synthesizes current knowledge and clinical progress in oncolytic virus therapy (OVT) as a component of modern cancer treatment.

Key points:

• Mechanism of action: Oncolytic viruses selectively infect and lyse tumor cells, inducing immunogenic cell death. This enhances tumor antigen presentation and can convert an immune-suppressive tumor microenvironment into an immune-permissive one, promoting systemic antitumor immunity.

• Biologic effects beyond lysis: OVs modulate tumor-associated processes including angiogenesis and extracellular matrix remodeling, disrupting tumor growth, invasion, and metastasis, and potentially impacting recurrence and resistance patterns.

• Virus classes and mechanisms: The review classifies different OV platforms and describes their multimodal mechanisms targeting tumorigenesis, metastatic spread, disease recurrence, and mechanisms of therapy resistance.

• Combination strategies: Substantial focus is placed on combinations of OVT with:
  • Chemotherapy
  • Radiotherapy
  • Immune checkpoint inhibitors
  • Adoptive cell therapies
  • Epigenetic-targeted agents

  These combinations can achieve synergy by increasing tumor selectivity, amplifying antitumor immune responses, and overcoming resistance to standard therapies.

• Clinical development and integration: The authors summarize clinical research progress where OVT is integrated into existing treatment paradigms, describing how these agents are being positioned alongside or within current standards of care.

• Challenges and barriers: The review highlights key obstacles limiting broad implementation, including:
  • Viral dissemination and pharmacokinetics in humans
  • Emergence of resistance
  • Manufacturing, safety, and regulatory complexities

• Future directions: Evidence-based strategies are proposed to optimize OVT, including rational combinations, better patient and tumor selection, improved viral engineering, and translational approaches to bridge preclinical success with clinical benefit.