Related Experiment Video

Updated: Oct 5, 2026

Simple and Fast Rolling Circle Amplification-Based Detection of Topoisomerase 1 Activity in Crude Biological Samples
10:13

Simple and Fast Rolling Circle Amplification-Based Detection of Topoisomerase 1 Activity in Crude Biological Samples

Published on: December 2, 2022

Expression and integrity of DNA topoisomerase II isoforms does not explain generic drug resistance in malignant

B R McLaren1, D Whitaker, B W Robinson

  • 1Western Australian Institute for Medical Research, University Department of Medicine, University of Western Australia, Perth, Australia.

Cancer Chemotherapy and Pharmacology
|August 8, 2001
PubMed
Abstract

Insights

Malignant mesothelioma exhibits resistance to chemotherapy, potentially due to topoisomerase II alterations. Mutations in topoisomerase IIalpha were linked to extreme resistance to etoposide in mesothelioma cell lines.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Research

Background:

  • Malignant mesothelioma is notoriously resistant to chemotherapy.
  • Mechanisms underlying this drug resistance are not well understood.
  • Topoisomerase II function/expression disruption is a potential cause of resistance.

Purpose of the Study:

  • To investigate the role of topoisomerase II isoforms in malignant mesothelioma drug resistance.
  • To assess topoisomerase II expression and mutations in mesothelioma.
  • To evaluate mesothelioma cell line sensitivity to topoisomerase-targeting drugs.

Main Methods:

  • Assessed topoisomerase II isoform expression in primary tumors.
  • Tested mesothelioma cell lines for sensitivity to doxorubicin and etoposide.
  • Sequenced topoisomerase genes and investigated other resistance mechanisms.

Main Results:

  • Topoisomerase II beta was more frequently expressed in primary tumors.
  • A point mutation in topoisomerase IIalpha was found in one etoposide-resistant cell line.
  • No correlation found between protein levels and drug sensitivity; mRNA variations did not explain resistance.

Conclusions:

  • Mutations in topoisomerase IIalpha can confer extreme etoposide resistance in mesothelioma.
  • Further research is needed to understand the general drug resistance of mesothelioma.

More Related Videos

Tropomodulin 3 Overexpression as a Marker for Platinum Resistance and Immune Infiltration in Ovarian Cancer09:40

Tropomodulin 3 Overexpression as a Marker for Platinum Resistance and Immune Infiltration in Ovarian Cancer

Published on: August 2, 2024

Related Concept Videos

DNA Topoisomerases02:02

DNA Topoisomerases

Topoisomerases are enzymes that relax overwound DNA molecules during various cell processes, including DNA replication and transcription. These enzymes regulate positive and negative DNA supercoiling without changing the nucleotide sequence. DNA overwinding in a clockwise direction results in positively supercoiled DNA, whereas underwinding in a counterclockwise direction produces negatively supercoiled DNA.
Types and Mechanism of action
Topoisomerases are divided into two main types.  Type I...
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...
Inhibitors of Bacterial DNA Synthesis01:28

Inhibitors of Bacterial DNA Synthesis

Bacterial pathogens depend on precise and efficient DNA replication to sustain infection. Two type II topoisomerases—DNA gyrase and topoisomerase IV—are critical to this process, as they resolve DNA supercoiling and unlink chromosomes during replication. Fluoroquinolones, synthetic derivatives of quinolones, exploit this mechanism by stabilizing the transient DNA–enzyme cleavage complex, preventing strand religation, and causing lethal double-strand breaks. These antibiotics are selectively...
Abnormal Proliferation02:23

Abnormal Proliferation

Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the daughter...
Electron Transport Chain: Complex I and II01:46

Electron Transport Chain: Complex I and II

The mitochondrial electron transport chain (ETC) is the main energy generation system in the eukaryotic cells. However, mitochondria also produce cytotoxic reactive oxygen species (ROS) due to the large electron flow during oxidative phosphorylation. While Complex I is one of the primary sources of superoxide radicals, ROS production by Complex II is uncommon and may only be observed in cancer cells with mutated complexes.
ROS generation is regulated and maintained at moderate levels necessary...
Pharmacogenetics of Drug Targets: β₂-Adrenergic Receptors, Apo E, Thymidylate Synthase01:11

Pharmacogenetics of Drug Targets: β₂-Adrenergic Receptors, Apo E, Thymidylate Synthase

Genetic polymorphisms in drug targets have emerged as critical determinants of interindividual variability in drug response and toxicity. Pharmacogenomic investigations increasingly focus on identifying these variations to personalize and optimize therapeutic interventions. A drug target may be a receptor, enzyme, or signaling protein involved in pharmacologic responses or disease-related pathways. While early pharmacogenetic studies focused primarily on drug metabolism, current research...