Related Experiment Video

Updated: May 7, 2026

Paramyxoviruses for Tumor-targeted Immunomodulation: Design and Evaluation Ex Vivo
12:42

Paramyxoviruses for Tumor-targeted Immunomodulation: Design and Evaluation Ex Vivo

Published on: January 7, 2019

DNA demethylating agents synergize with oncolytic HSV1 against malignant gliomas

Kazuo Okemoto1, Kazue Kasai, Benjamin Wagner

  • 1Authors' Affiliations: Dardinger Center for Neuro-oncology and Neurosciences, Department of Neurological Surgery, James Cancer Hospital/Solove Research Institute/Comprehensive Cancer Center and Wexner Medical Center; Center for Biostatistics, The Ohio State University, Columbus, Ohio; and Department of Neurosurgery Institute for the Neurosciences at the Brigham, Brigham and Women's/Faulkner Hospital and Center for Neuro-oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.

Clinical Cancer Research : an Official Journal of the American Association for Cancer Research
|September 24, 2013
PubMed
Abstract

Insights

Demethylating agents enhance oncolytic virus (OV) therapy for malignant glioma by overcoming promoter methylation. Combining these agents with rQNestin34.5 improved tumor cell lysis and prolonged survival in preclinical models.

Area of Science:

  • Oncolytic virotherapy
  • Cancer epigenetics
  • Neuro-oncology

Background:

  • Oncolytic viruses (OV) based on herpes simplex virus type 1 (HSV1) show promise for cancer treatment.
  • The engineered OV, rQNestin34.5, targets malignant glioma via a nestin promoter.
  • Promoter methylation in infected glioma cells reduces the efficacy of rQNestin34.5.

Purpose of the Study:

  • To investigate if demethylating agents can improve the efficacy of rQNestin34.5 therapy.
  • To evaluate the combination of demethylating drugs with rQNestin34.5 in malignant glioma models.

Main Methods:

  • Utilized demethylating drugs: 5-azacytidine (5-Aza), decitabine, and valproic acid (VPA).
  • Tested therapies in both in vitro and in vivo malignant glioma models.
  • Assessed OV replication, tumor cell lysis, and animal survival.

Main Results:

  • Demethylating agents, particularly 5-Aza, enhanced OV replication and glioma cell lysis in vitro.
  • 5-Aza demonstrated synergistic effects with rQNestin34.5 in vitro.
  • Combination therapy with 5-Aza or decitabine and rQNestin34.5 significantly prolonged survival in mice with human glioma xenografts.

Conclusions:

  • Demethylating agents can overcome rQNestin34.5 promoter methylation, thereby enhancing its efficacy.
  • The combination of demethylating agents and rQNestin34.5 warrants further investigation in preclinical and clinical settings for malignant glioma.

More Related Videos

Evaluating In Vitro DNA Damage Using Comet Assay10:43

Evaluating In Vitro DNA Damage Using Comet Assay

Published on: October 11, 2017

Growth, Purification, and Titration of Oncolytic Herpes Simplex Virus06:14

Growth, Purification, and Titration of Oncolytic Herpes Simplex Virus

Published on: May 13, 2021

Related Concept Videos

Tumor Immunotherapy01:27

Tumor Immunotherapy

Immunotherapy is a treatment that boosts or manipulates the immune system to fight diseases, including cancer. For instance, by stimulating an immune response through vaccinations against viruses that cause cancers, like hepatitis B virus and human papillomavirus, these diseases can be prevented. Nonetheless, some cancer cells can avoid the immune system due to their rapid mutation and division. The immune response to many cancers involves three phases: elimination, equilibrium, and escape.
Cancer Therapies02:49

Cancer Therapies

Cancer therapies are various modes of treatment, such as surgery, radiation therapy, and chemotherapy that are administered to cancer patients.
However, cancer treatments can pose several challenges, as therapies used to kill cancer cells are generally also toxic to normal cells. Moreover, cancer cells mutate rapidly and can develop resistance to chemical agents or radiation therapy. Besides, all types of cancer cells may not respond to the same therapy. Some cancer cells respond to one...
Combination Therapies and Personalized Medicine02:50

Combination Therapies and Personalized Medicine

Combining two or more treatment methods increases the life span of cancer patients while reducing damage to vital organs or tissue from the overuse of a single treatment. Combination therapy also targets different cancer-inducing pathways, thus reducing the chances of developing resistance to treatment.
The combination of the drug acetazolamide and sulforaphane is a good example of combination therapy to treat cancer. The cells in the interior of a large tumor often die due to the hypoxic and...
Targeted Cancer Therapies02:57

Targeted Cancer Therapies

The targeted cancer therapies, also known as “molecular targeted therapies,” take advantage of the molecular and genetic differences between the cancer cells and the normal cells. It needs a thorough understanding of the cancer cells to develop drugs that can target specific molecular aspects that drive the growth, progression, and spread of cancer cells without affecting the growth and survival of other normal cells in the body.
There are several types of targeted therapies against specific...
Targeted Cancer Therapies02:57

Targeted Cancer Therapies

The targeted cancer therapies, also known as “molecular targeted therapies,” take advantage of the molecular and genetic differences between the cancer cells and the normal cells. It needs a thorough understanding of the cancer cells to develop drugs that can target specific molecular aspects that drive the growth, progression, and spread of cancer cells without affecting the growth and survival of other normal cells in the body.
There are several types of targeted therapies against specific...