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Genome-wide RNAi Screening to Identify Host Factors That Modulate Oncolytic Virus Therapy
Published on: April 3, 2018
Targeted Metabolic Reprogramming to Improve the Efficacy of Oncolytic Virus Therapy
Barry E Kennedy1, Maryanne Sadek1, Shashi A Gujar2
1Department of Pathology, Dalhousie University, Halifax, NS B3H 1X5, Canada.
Abstract:
Oncolytic viruses (OVs) represent a promising new class of cancer therapeutics and cause antitumor effects by two major mechanisms: (1) directly killing cancer cells in a process known as oncolysis, or (2) initiating a powerful antitumor immune response. Interestingly, energy metabolism, within either cancer cells or immune cells, plays a pivotal role in defining the outcome of OV-mediated antitumor effects. Following therapeutic administration, OVs must hijack host cell metabolic pathways to acquire building blocks such as nucleotides, lipids, and amino acids for the process of replication that is necessary for oncolysis. Additionally, OV-stimulated antitumor immune responses are highly dependent on the metabolic state within the tumor microenvironment. Thus, metabolic reprogramming strategies bear the potential to enhance the efficacy of both OV-mediated oncolysis and antitumor immune responses.
Insights
Oncolytic viruses (OVs) are novel cancer therapies that kill tumors directly or stimulate immune responses. Optimizing cancer cell and immune cell metabolism can enhance OV efficacy.
Area of Science:
- Oncology
- Virology
- Metabolic Engineering
Background:
- Oncolytic viruses (OVs) are emerging cancer therapeutics with dual antitumor mechanisms: direct cancer cell lysis (oncolysis) and immune system activation.
- The effectiveness of OVs is significantly influenced by the metabolic state of both cancer cells and immune cells within the tumor microenvironment.
Purpose of the Study:
- To explore the critical role of cellular energy metabolism in OV-mediated antitumor effects.
- To investigate how metabolic reprogramming can enhance the efficacy of OV-based cancer therapies.
Main Methods:
- This study reviews the mechanisms by which OVs interact with host cell metabolism.
- It examines the metabolic requirements for OV replication and oncolysis.
- It analyzes the impact of the tumor microenvironment's metabolic state on OV-induced immune responses.
Main Results:
- OVs require hijacking host cell metabolic pathways for replication and oncolysis, utilizing building blocks like nucleotides and lipids.
- Antitumor immune responses triggered by OVs are highly dependent on the metabolic conditions within the tumor microenvironment.
- Metabolic reprogramming strategies show potential for improving OV therapeutic outcomes.
Conclusions:
- Cellular energy metabolism is a key determinant of oncolytic virus efficacy.
- Targeting metabolic pathways presents a promising strategy to enhance both oncolysis and antitumor immunity for improved cancer treatment.
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