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Updated: Oct 30, 2025

Assessment of Global DNA Double-Strand End Resection using BrdU-DNA Labeling coupled with Cell Cycle Discrimination Imaging
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Analyzing the Opportunities to Target DNA Double-Strand Breaks Repair and Replicative Stress Responses to Improve

Paula Pellenz Tomasini1,2, Temenouga Nikolova Guecheva3, Natalia Motta Leguisamo1

  • 1Laboratory of Genetic Toxicology, Federal University of Health Sciences of Porto Alegre, Avenida Sarmento Leite, 245, Porto Alegre 90050-170, Brazil.

Cancers
|July 2, 2021
PubMed

Insights

Targeting DNA repair and replication stress response pathways offers a novel synthetic lethal strategy for colorectal cancer (CRC). This approach exploits DNA damage response (DDR) defects to improve treatment outcomes for metastatic CRC patients.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Current colorectal cancer (CRC) treatments, especially for metastatic disease, have limited efficacy and face challenges with treatment resistance.
  • Conventional chemotherapy and existing targeted agents/immunotherapy combinations show unsatisfactory outcomes in the metastatic setting.

Purpose of the Study:

  • To explore the potential of targeting DNA repair and replication stress response pathways in CRC.
  • To investigate synthetic lethal strategies that exploit DNA damage response (DDR) pathway defects in colorectal cancer.

Main Methods:

  • Reviewing therapeutic agents targeting DNA double-strand break (DSB) repair pathways (homologous recombination, NHEJ, MMEJ).
  • Examining inhibitors of base excision repair (BER) protein poly (ADP-ribose) polymerase (PARP).
  • Analyzing inhibitors of DNA damage kinases like ATR, CHK1, WEE1, and ATM.

Main Results:

  • The study identifies multiple DDR pathways and their inhibitors as potential therapeutic targets in CRC.
  • Exploiting synthetic lethality through DDR inhibition is a promising, yet underexplored, strategy for CRC.

Conclusions:

  • Targeting DNA repair and replication stress response mechanisms presents a novel therapeutic avenue for colorectal cancer.
  • Further research into DDR-targeting agents and associated biomarkers is crucial for improving outcomes in metastatic CRC.
Keywords:
DNA double strand break repaircolorectal cancerreplication stresstarget therapy

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