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Quantifying Replication Stress in Ovarian Cancer Cells Using Single-Stranded DNA Immunofluorescence
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Targeting replication stress in cancer therapy

Alexandre André B A da Costa1, Dipanjan Chowdhury1, Geoffrey I Shapiro2

  • 1Department of Radiation Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.

Nature Reviews. Drug Discovery
|October 6, 2022
PubMed

Insights

Targeting cancer

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Replication stress drives genomic instability and is a key vulnerability in cancer cells.
  • Checkpoint kinases like ATR, CHK1, WEE1, and MYT1 regulate the DNA damage response and cell cycle.
  • Inhibiting these kinases can trigger innate immune responses via cytoplasmic DNA fragments.

Purpose of the Study:

  • To review current and emerging strategies for targeting replication stress in cancer.
  • To discuss the therapeutic potential of inhibiting DNA damage response kinases.
  • To explore combinations of replication stress inhibitors with other cancer therapies.

Main Methods:

  • Review of preclinical research on replication stress targeting.
  • Analysis of clinical trial data for ATR, CHK1, WEE1, and MYT1 inhibitors.
  • Examination of biomarker development for patient stratification.

Main Results:

  • Multiple inhibitors targeting ATR, CHK1, WEE1, and MYT1 are in clinical trials.
  • Combinations with chemotherapy, PARP inhibitors, and immune checkpoint inhibitors are being evaluated.
  • Targeting replication stress aims to exploit cancer vulnerabilities and enhance anti-tumor immunity.

Conclusions:

  • Targeting replication stress is a promising therapeutic avenue in oncology.
  • Combination therapies hold potential for overcoming resistance and improving treatment efficacy.
  • Further research and clinical evaluation are crucial for optimizing these strategies.

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