Related Experiment Video

Updated: May 22, 2025

A Method for Screening and Validation of Resistant Mutations Against Kinase Inhibitors
12:40

A Method for Screening and Validation of Resistant Mutations Against Kinase Inhibitors

Published on: December 7, 2014

14.8K

IP6K2 mutations as a novel mechanism of resistance to oncolytic virus therapy

Zhijian Huang1,2,3, Xiangqian Zhao4,5, Zirong Jiang6

  • 1Department of Breast Surgical Oncology, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou, 350014, China.

Journal of Translational Medicine
|March 13, 2025
PubMed
Abstract

Insights

Inositol Hexakisphosphate Kinase 2 (IP6K2) is crucial for oncolytic virus therapy (OVT) efficacy. Loss of IP6K2 confers resistance to Herpes Simplex Virus Type 1 (HSV-1) treatment, indicating its potential as a predictive biomarker.

Area of Science:

  • Oncolytic virotherapy
  • Cancer genomics
  • Molecular oncology

Background:

  • Oncolytic virus therapy (OVT) shows promise but faces challenges due to variable patient responses and resistance.
  • Identifying biomarkers for patient stratification is essential for optimizing OVT efficacy.

Purpose of the Study:

  • To investigate the role of Inositol Hexakisphosphate Kinase 2 (IP6K2) in Herpes Simplex Virus Type 1 (HSV-1) oncolysis.
  • To determine if IP6K2 status influences resistance to OVT.

Main Methods:

  • CRISPR/Cas9 was used to knock out the IP6K2 gene.
  • In vitro assays assessed apoptosis, cell proliferation, and viral attachment.
  • A subcutaneous xenograft model evaluated in vivo efficacy.
  • Pan-cancer genomic analysis utilized cBioPortal and TCGA databases.

Main Results:

  • IP6K2 is essential for HSV-1 replication and virus-induced apoptosis via the p53/p21 pathway.
  • IP6K2-deficient tumors showed resistance to HSV-1 oncolysis in vivo.
  • Genomic analysis revealed potential IP6K2 mutations associated with resistance across multiple cancer types.

Conclusions:

  • IP6K2 acts as a key determinant of OVT response.
  • Assessing pre-treatment IP6K2 status may enable personalized OVT strategies.
  • IP6K2 is a potential biomarker for predicting OVT resistance.
Keywords:
Cancer treatmentsHSV-1 oncolytic virusInositol hexakisphosphate kinase 2Resistance

More Related Videos

Genome-wide RNAi Screening to Identify Host Factors That Modulate Oncolytic Virus Therapy08:51

Genome-wide RNAi Screening to Identify Host Factors That Modulate Oncolytic Virus Therapy

Published on: April 3, 2018

9.0K
An In Vitro Model for Studying Cellular Transformation by Kaposi Sarcoma Herpesvirus09:53

An In Vitro Model for Studying Cellular Transformation by Kaposi Sarcoma Herpesvirus

Published on: August 25, 2017

8.2K

Related Concept Videos

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...
3.2K
Cytotoxic T Cells-mediated Immune Response01:27

Cytotoxic T Cells-mediated Immune Response

Cytotoxic T cells are a vital component of the immune system. They have the remarkable ability to identify and target antigens on infected or abnormal cells. These antigens often originate from intracellular pathogens such as viruses or abnormal proteins cancer cells produce.
Immunological surveillance is the ability of immune cells to monitor and eliminate infected cells with intracellular pathogens, neoplastically transformed cells, and cells with non-self antigens. Cytotoxic T cells and NK...
823
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...
7.5K
Viral Mutations00:36

Viral Mutations

A mutation is a change in the sequence of bases of DNA or RNA in a genome. Some mutations occur during replication of the genome due to errors made by the polymerase enzymes that replicate DNA or RNA. Unlike DNA polymerase, RNA polymerase is prone to errors because it is not capable of “proofreading” its work. Viruses with RNA-based genomes, like HIV, therefore accrue mutations faster than viruses with DNA-based genomes. Because mutation and recombination provide the raw material...
32.1K
Rous Sarcoma Virus (RSV) and Cancer01:03

Rous Sarcoma Virus (RSV) and Cancer

Rous Sarcoma virus or RSV was discovered by F. Peyton Rous in the year 1911 as a filterable transmissible agent that could cause tumors in chickens. He won a Nobel Prize for this discovery in 1966. His experiments clearly demonstrated that some cancers could be caused by infectious agents and led to the discovery of many more cancer-causing viruses in animals as well as humans.
RSV is a retrovirus that contains two copies of a plus-strand  RNA genome. Its genome consists of four main open...
4.9K
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.
457