Related Experiment Video

Updated: Dec 5, 2025

Implementation of In Vitro Drug Resistance Assays: Maximizing the Potential for Uncovering Clinically Relevant Resistance Mechanisms
08:46

Implementation of In Vitro Drug Resistance Assays: Maximizing the Potential for Uncovering Clinically Relevant Resistance Mechanisms

Published on: December 9, 2015

11.0K

Assessing and Overcoming Resistance Phenomena against a Genetically Modified Vaccinia Virus in Selected Cancer Cell

Susanne Berchtold1,2, Julia Beil1,2,3, Christian Raff1

  • 1Department of Internal Medicine VIII, University Hospital Tübingen, D-72076 Tübingen, Germany.

International Journal of Molecular Sciences
|October 20, 2020
PubMed

Insights

Genetically modified vaccinia viruses (VACVs) show oncolytic potential. Combining VACVs with a prodrug system effectively overcomes tumor cell resistance, enhancing cancer virotherapy efficacy.

Area of Science:

  • Oncology
  • Virology
  • Genetics

Background:

  • Genetically modified vaccinia viruses (VACVs) exhibit significant oncolytic properties for cancer treatment.
  • Tumor cell resistance to VACVs poses a challenge to their widespread clinical application.
  • Novel strategies are needed to enhance the efficacy of VACV-based virotherapy.

Purpose of the Study:

  • To investigate primary resistance mechanisms of NCI-60 tumor cell lines to the oncolytic vaccinia virus GLV-1h94.
  • To evaluate the efficacy of a combination therapy involving GLV-1h94 and the prodrug 5-fluorocytosine (5-FC).
  • To understand the role of the virus-encoded super cytosine deaminase (SCD) enzyme in overcoming tumor resistance.

Main Methods:

  • Utilized cell mass assays, viral replication studies, and fluorescence microscopy.
  • Tested susceptibility of NCI-60 cell lines to GLV-1h94 alone and in combination with 5-FC.
  • Analyzed the interaction between GLV-1h94, SCD, 5-FC, and tumor cell sensitivity.

Main Results:

  • GLV-1h94 alone resulted in high susceptibility in only 50% of tested cell lines.
  • Combination therapy with 5-FC increased susceptibility to 85% of cell lines, with no high-grade resistance observed.
  • The cytotoxic effect of 5-fluorouracil (5-FU) depended on the balance between viral oncolysis susceptibility and 5-FU sensitivity.

Conclusions:

  • Virus-encoded prodrug systems, like SCD converting 5-FC to 5-FU, can effectively overcome cellular resistance to VACV virotherapy.
  • Combination therapy demonstrates broad potential for treating various tumor types.
  • Further clinical trials (Phase I/II) are recommended to explore the therapeutic potential of this approach.
Keywords:
5-fluorocytosineNCI-60 tumor cell panelchemovirotherapyoncolytic virotherapysuper cytosine deaminase prodrug systemvaccinia virusvirotherapy resistance

More Related Videos

Establishing Dual Resistance to EGFR-TKI and MET-TKI in Lung Adenocarcinoma Cells In Vitro with a 2-step Dose-escalation Procedure09:38

Establishing Dual Resistance to EGFR-TKI and MET-TKI in Lung Adenocarcinoma Cells In Vitro with a 2-step Dose-escalation Procedure

Published on: August 11, 2017

9.1K
Evaluating the Effectiveness of Cancer Drug Sensitization In Vitro and In Vivo09:19

Evaluating the Effectiveness of Cancer Drug Sensitization In Vitro and In Vivo

Published on: February 6, 2015

9.0K

Related Concept Videos

Cancer Vaccines01:30

Cancer Vaccines

Cancer treatment vaccines are a rapidly evolving field that offers a promising approach to immunotherapy. Unlike traditional vaccines that prevent diseases, cancer treatment vaccines are designed to treat existing cancers by stimulating the immune system to recognize and attack cancer cells.
Cancer vaccines come in two categories: preventive (prophylactic) and treatment (active). Preventive vaccines, such as the Human Papillomavirus (HPV) vaccine, protect against viruses that cause certain...
837
Treatment Resistant Cancers02:56

Treatment Resistant Cancers

Cancer is the second leading cause of death in the United States. A cancer cell is genetically unstable and hence can mutate faster. They can also modify their microenvironment and escape immune surveillance. The difficulties in treating cancer are further compounded by the emergence of rapid resistance to anticancer drugs. The most common ways to attain resistance in cancer cells include alteration in drug transport and metabolism, modification of drug target, elevated DNA damage response, or...
3.6K
Cell Lines01:16

Cell Lines

A cell line is a population of cells grown in vitro that can be subcultured over several generations. Normal cells cease to divide after a certain number of cell divisions, a process known as replicative senescence. This number, called the Hayflick limit, was conceptualized by Leonard Hayflick in 1961 when he observed that fetal cells grown in culture could only divide 40-60 times. This limit is due to the shortening of the telomeres during each round of cell division, preventing cell division...
9.7K