Related Experiment Video

Updated: Oct 30, 2025

Dual CRISPR-Interference Strategy for Targeting Synthetic Lethal Interactions Between Non-Coding RNAs in Cancer Cells
07:23

Dual CRISPR-Interference Strategy for Targeting Synthetic Lethal Interactions Between Non-Coding RNAs in Cancer Cells

Published on: May 30, 2025

795

VLX600 Disrupts Homologous Recombination and Synergizes with PARP Inhibitors and Cisplatin by Inhibiting Histone

Thomas L Ekstrom1, Nicholas M Pathoulas1, Amelia M Huehls1

  • 1Division of Oncology Research, Mayo Clinic College of Medicine, Mayo Clinic, Rochester, Minnesota.

Molecular Cancer Therapeutics
|July 5, 2021
PubMed

Insights

VLX600 disrupts homologous recombination (HR) DNA repair, sensitizing ovarian cancer cells to standard therapies. This iron chelator targets histone lysine demethylases (KDMs), offering a novel strategy for HR-proficient tumors.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Therapeutics

Background:

  • Tumors with defective homologous recombination (HR) DNA repair are sensitive to platinum agents and PARP inhibitors (PARPis).
  • HR-proficient tumors exhibit limited sensitivity to these therapies.
  • Disrupting HR could enhance treatment efficacy in HR-proficient cancers.

Purpose of the Study:

  • To investigate the efficacy of VLX600, a Phase I clinical trial agent, in disrupting HR.
  • To determine if VLX600 synergizes with PARPis and platinum compounds in ovarian cancer.
  • To elucidate the mechanism by which VLX600 disrupts HR.

Main Methods:

  • Utilized ovarian cancer cell lines.
  • Administered VLX600, PARPis, and platinum compounds.
  • Assessed HR disruption and protein recruitment.
  • Investigated the role of iron-dependent histone lysine demethylases (KDMs).

Main Results:

  • VLX600 demonstrated HR disruption in ovarian cancer cells.
  • VLX600 synergized with PARPis and platinum compounds.
  • VLX600 inhibits iron-dependent KDMs, blocking HR repair protein (e.g., RAD51) recruitment to DNA breaks.

Conclusions:

  • VLX600 induces HR defects, sensitizing HR-proficient ovarian cancers to platinum agents and PARPis.
  • Pharmacological targeting of KDMs with VLX600 represents a potential therapeutic strategy.
  • This approach may overcome resistance to standard-of-care therapies in ovarian cancer.

More Related Videos

Laser Microirradiation to Study In Vivo Cellular Responses to Simple and Complex DNA Damage10:44

Laser Microirradiation to Study In Vivo Cellular Responses to Simple and Complex DNA Damage

Published on: January 31, 2018

10.4K
Tools to Study the Role of Architectural Protein HMGB1 in the Processing of Helix Distorting, Site-specific DNA Interstrand Crosslinks12:19

Tools to Study the Role of Architectural Protein HMGB1 in the Processing of Helix Distorting, Site-specific DNA Interstrand Crosslinks

Published on: November 10, 2016

8.5K

Related Concept Videos

Homologous Recombination02:31

Homologous Recombination

The basic reaction of homologous recombination (HR) involves two chromatids that contain DNA sequences sharing a significant stretch of identity. One of these sequences uses a strand from another as a template to synthesize DNA in an enzyme-catalyzed reaction. The final product is a novel amalgamation of the two substrates. To ensure an accurate recombination of sequences, HR is restricted to the S and G2 phases of the cell cycle. At these stages, the DNA has been replicated already and the...
57.0K
Homologous Recombination02:31

Homologous Recombination

5.2K
Conservative Site-specific Recombination and Phase Variation02:53

Conservative Site-specific Recombination and Phase Variation

Because the DNA segments are cut and reorganized in a direction-specific manner, site-specific recombination has emerged as an efficient genetic engineering technique. Flippase and Cyclization recombinases or Flp and Cre, respectively, are two members of the tyrosine recombinase family derived from bacteriophages, that are used to mediate site-specific DNA insertions, deletions, and targeted expression of proteins in mammalian cell lines.
The recognition sites for Cre recombinase called LoxP...
6.3K
Crossing Over01:30

Crossing Over

Crossing over is the exchange of genetic information between homologous chromosomes during prophase I of meiosis I. Genetic recombination gives rise to allelic diversity in the newly formed daughter cells. In humans, crossing over produces genetically distinct haploid egg and sperm cells that undergo fertilization to produce unique offspring. Before cell division starts, the germ cell’s chromosome(s) undergo duplication in the S phase of the cell cycle. As the cells enter prophase I,...
5.2K
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...
8.0K
Long-patch Base Excision Repair01:02

Long-patch Base Excision Repair

Since the discovery of the two BER pathways, there has been a debate about how a cell chooses one pathway over the other and the factors determining this selection. Numerous in vitro experiments have pointed out multiple determinants for the sub-pathway selection. These are:
7.4K