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Updated: Sep 22, 2025

Visualizing and Quantifying Endonuclease-Based Site-Specific DNA Damage
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Targeting the DNA damage response and repair in cancer through nucleotide metabolism

Thomas Helleday1,2, Sean G Rudd1

  • 1Science for Life Laboratory, Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden.

Molecular Oncology
|May 18, 2022
PubMed

Insights

Targeting nucleotide metabolism enzymes can selectively harm cancer cells by inducing DNA damage. This strategy enhances chemotherapy effectiveness, offering new avenues for cancer treatment.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Cancer Research

Background:

  • Cancer cells rely on DNA damage response and repair mechanisms.
  • Deoxynucleoside triphosphates (dNTPs) are essential for DNA replication and repair, supplied by nucleotide metabolic pathways.
  • Enzymes in nucleotide metabolism are potential targets for cancer therapy.

Purpose of the Study:

  • To review strategies targeting deoxynucleoside triphosphate (dNTP) metabolic enzymes for cancer treatment.
  • To explore how targeting these enzymes can induce DNA damage in cancer cells.
  • To discuss the role of dNTP metabolic enzymes in enhancing chemotherapy.

Main Methods:

  • Review of existing literature on DNA damage response, DNA repair, and nucleotide metabolism in cancer.
  • Analysis of the role of specific enzymes like MTH1, MTHFD2, and SAMHD1.
  • Discussion of antimetabolite chemotherapies and their interaction with nucleotide metabolism.

Main Results:

  • Targeting dNTP metabolic enzymes can selectively induce toxic DNA lesions in cancer cells.
  • These pathways are crucial for activating antimetabolites, a key class of chemotherapies.
  • Enzyme targeting can refine the use of existing chemotherapeutics.

Conclusions:

  • Exploiting nucleotide metabolism offers a promising anticancer strategy.
  • Targeting enzymes like MTH1, MTHFD2, and SAMHD1 can enhance cancer cell vulnerability.
  • This approach holds potential for improving standard cancer care.
Keywords:
DNA damage responseMTH1MTHFD2SAMHD1cancerdNTP metabolism

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