Related Experiment Video

Updated: Mar 11, 2026

Testing Targeted Therapies in Cancer using Structural DNA Alteration Analysis and Patient-Derived Xenografts
10:27

Testing Targeted Therapies in Cancer using Structural DNA Alteration Analysis and Patient-Derived Xenografts

Published on: July 25, 2020

8.0K

Targeting PRMTs Creates Vulnerability of DNA Double-Stand Break Repair Pathways, and Potentiates Chemotherapy

Charlène Thiebaut1,2,3, Sébastien Martinez1,2,3, Ludivine Pruvost1,2,3

  • 1Université Claude Bernard Lyon 1, Lyon, France.

Cancer Science
|March 9, 2026
PubMed

Insights

Targeting protein arginine methyltransferases (PRMT1 and PRMT5) can enhance chemotherapy efficacy in triple-negative breast cancer (TNBC). Inhibiting PRMTs sensitizes resistant TNBC cells to DNA-damaging agents, offering a new therapeutic strategy.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Therapeutics

Background:

  • Triple-negative breast cancer (TNBC) often exhibits resistance to DNA-damaging chemotherapies due to upregulated DNA repair mechanisms.
  • Protein arginine methyltransferases (PRMT1 and PRMT5) play a role in DNA repair pathways, maintaining genomic integrity.

Purpose of the Study:

  • To investigate whether inhibiting PRMT1 and PRMT5 can sensitize TNBC cells to DNA double-strand break-inducing chemotherapies.
  • To explore the role of PRMT1 and PRMT5 in DNA repair pathways relevant to TNBC treatment.

Main Methods:

  • Assessed PRMT1 and PRMT5 recruitment to DNA double-strand breaks induced by doxorubicin or carboplatin.
  • Evaluated the effect of combining PRMT inhibitors with chemotherapy on TNBC cell proliferation and clonogenicity in vitro.
  • Tested the efficacy of carboplatin combined with PRMT inhibitors in patient-derived TNBC models.

Main Results:

  • PRMT1 and PRMT5 were recruited to DNA double-strand breaks following doxorubicin or carboplatin treatment.
  • PRMT1 and PRMT5 are involved in the homologous recombination repair pathway.
  • Combination therapy increased DNA damage, impaired TNBC cell growth, and sensitized patient-derived models to carboplatin.

Conclusions:

  • Targeting PRMT1 and PRMT5 enzymatic activity can enhance the efficacy of DNA-damaging chemotherapies in TNBC.
  • PRMT inhibitors show promise as combinatorial agents to overcome chemotherapy resistance in TNBC.
  • Preclinical data support the clinical evaluation of PRMT inhibitors for TNBC treatment.
Keywords:
DNA‐damage repairPRMT1PRMT5arginine methylationtriple‐negative breast cancer

More Related Videos

Quantitative Methods to Study Protein Arginine Methyltransferase 1-9 Activity in Cells08:11

Quantitative Methods to Study Protein Arginine Methyltransferase 1-9 Activity in Cells

Published on: August 7, 2021

4.7K
Assessment of Global DNA Double-Strand End Resection using BrdU-DNA Labeling coupled with Cell Cycle Discrimination Imaging06:44

Assessment of Global DNA Double-Strand End Resection using BrdU-DNA Labeling coupled with Cell Cycle Discrimination Imaging

Published on: April 28, 2021

4.7K

Related Concept Videos

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...
60
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...
9.0K
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...
3.9K
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...
5.4K
Mismatch Repair01:20

Mismatch Repair

Organisms are capable of detecting and fixing nucleotide mismatches that occur during DNA replication. This sophisticated process requires identifying the new strand and replacing the erroneous bases with correct nucleotides. Mismatch repair is coordinated by many proteins in both prokaryotes and eukaryotes.
The Mutator Protein Family Plays a Key Role in DNA Mismatch Repair
The human genome has more than 3 billion base pairs of DNA per cell. Prior to cell division, that vast amount of genetic...
6.8K
Mismatch Repair01:36

Mismatch Repair

Overview
44.5K