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Updated: Oct 3, 2025

A High-Throughput Enzyme-Coupled Activity Assay to Probe Small Molecule Interaction with the dNTPase SAMHD1
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A High-Throughput Enzyme-Coupled Activity Assay to Probe Small Molecule Interaction with the dNTPase SAMHD1

Published on: April 16, 2021

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Modulation of DNA Damage Response by SAM and HD Domain Containing Deoxynucleoside Triphosphate Triphosphohydrolase

Eudald Felip1,2,3, Lucía Gutiérrez-Chamorro1, Maica Gómez4

  • 1AIDS Research Institute-IrsiCaixa, IGTP (Health Research Institute Germans Trias i Pujol), Hospital Germans Trias i Pujol, Universitat Autònoma de Barcelona, 08916 Badalona, Spain.

Cancers
|February 15, 2022
PubMed

Insights

Low expression of SAMHD1 (a key enzyme in DNA regulation) is linked to better outcomes in breast, ovarian, and lung cancer patients. This suggests SAMHD1 is a promising target for improving cancer therapies.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • SAMHD1 (deoxynucleotide triphosphate triohydrolase) regulates cell proliferation and apoptosis by controlling intracellular dNTP levels and DNA damage response.
  • The role of SAMHD1 in the evolution of solid tumors remains largely unexplored.

Purpose of the Study:

  • To investigate the prognostic and predictive value of SAMHD1 expression in advanced solid tumors.
  • To elucidate the underlying mechanisms of SAMHD1 function in cancer through in vitro models.

Main Methods:

  • Analysis of SAMHD1 expression in 128 advanced solid tumor patient samples treated with platinum derivatives and/or antimetabolites.
  • Development of in vitro SAMHD1 knock-out models to study its functional role.
  • Assessment of DNA damage markers (γ-H2AX) and apoptosis induction.

Main Results:

  • Low or absent SAMHD1 expression correlated with a positive prognosis in breast, ovarian, and non-small cell lung cancer (NSCLC) patients.
  • Low SAMHD1 expression predicted a better response to antimetabolites combined with platinum derivatives in NSCLC and ovarian cancer.
  • In vitro, SAMHD1 depletion led to increased γ-H2AX and apoptosis, indicating induced DNA damage and cell death.
  • Combined SAMHD1 depletion and platinum-based drugs showed synergistic effects in vitro.

Conclusions:

  • SAMHD1 expression is a significant prognostic and predictive biomarker in solid tumors.
  • Targeting SAMHD1 function presents a promising strategy for enhancing cancer therapy efficacy.
Keywords:
NSCLCSAMHD1breast cancerovarian cancersolid tumors

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