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Updated: Aug 9, 2026
Ex Vivo Infection of Live Tissue with Oncolytic Viruses
Published on: June 25, 2011
Viruses - seeking and destroying the tumor program
1Cancer Research Institute, University of California San Francisco, 94115, USA. coshea@cc.ucsf.edu
Abstract:
DNA viruses have enormous utility in cancer research, both as tools for tumor target discovery as well as agents for lytic cancer therapies. This is because there is a profound functional overlap between the DNA viral and tumor cell programs. DNA viruses encode proteins that elicit growth deregulation in infected cells similar to that engendered by mutations in tumor cells. Evolution has refined viral proteins to target the critical cellular hubs that regulate growth. Thus, viral proteins are discriminating biochemical probes that can be used to identify and characterize novel tumor targets. Moreover, the overlap between the DNA viral and tumor programs can also be exploited for the development of lytic cancer therapies. Discovering whether tumor cells selectively complement the replication of viral mutants can reveal novel oncolytic viral therapies, as well as unexpected tumor properties. For example, altered RNA export was recently uncovered as a novel tumor cell property that underlies ONYX-015 replication, a promising oncolytic adenoviral therapy. A perspective is provided on how adenovirus could be systematically exploited to map the requisite role, or indeed the redundancy, of cellular pathways that act in an integrated program to elicit pathological replication. This knowledge has important applications for the rational design of the next generation of oncolytic viruses, as well as the discovery of efficacious combination cancer therapies.
Insights
DNA viruses are valuable tools in cancer research for identifying tumor targets and developing lytic cancer therapies due to functional overlaps between viral and tumor cell programs. Exploiting these overlaps can lead to novel oncolytic viruses and combination cancer treatments.
Area of Science:
- Oncology
- Virology
- Molecular Biology
Background:
- DNA viruses share functional overlaps with tumor cell programs, enabling their use in cancer research.
- Viral proteins target critical cellular growth regulators, serving as probes for tumor target discovery.
- The interplay between viral and tumor cell processes can be leveraged for developing oncolytic cancer therapies.
Purpose of the Study:
- To explore the utility of DNA viruses in cancer research for target discovery and oncolytic therapy development.
- To investigate how tumor cells complement viral replication, revealing novel therapeutic strategies and tumor properties.
- To provide a perspective on exploiting adenoviruses for mapping cellular pathways crucial for pathological replication.
Main Methods:
- Analyzing the functional overlap between DNA viral and tumor cell programs.
- Investigating tumor cell complementation of viral mutant replication.
- Systematically exploiting adenovirus to map cellular pathway roles in viral replication.
Main Results:
- DNA viruses serve as effective tools for identifying and characterizing novel tumor targets.
- Tumor cell properties, such as altered RNA export, can underlie oncolytic viral therapy efficacy (e.g., ONYX-015).
- Understanding cellular pathway requirements for viral replication aids in designing next-generation oncolytic viruses.
Conclusions:
- DNA viruses offer significant potential for both cancer target discovery and the development of lytic cancer therapies.
- Exploiting the relationship between viruses and cancer cells can uncover new oncolytic viral therapies and therapeutic targets.
- This research informs the rational design of advanced oncolytic viruses and effective combination cancer treatments.
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