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Updated: Sep 10, 2025

A Data Integration Workflow to Identify Drug Combinations Targeting Synthetic Lethal Interactions
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A Data Integration Workflow to Identify Drug Combinations Targeting Synthetic Lethal Interactions

Published on: May 27, 2021

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Synthetic Lethality-Based Targets and Their Exploration in Tumour Combination Strategies

Lingya Wu1, Yixuan Deng1, Zhe Lei1

  • 1Department of Pathology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China.

Journal of Cellular and Molecular Medicine
|August 27, 2025
PubMed

Insights

Synthetic lethality (SL) offers new cancer treatments for undruggable targets and drug resistance. Emerging targets like ATR, WEE1, and WRN show promise, enhancing precision medicine.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Synthetic lethality (SL) provides novel therapeutic strategies for cancer, overcoming resistance to traditional therapies.
  • SL targets previously 'undruggable' genes, including tumor suppressor genes with deletion mutations.

Purpose of the Study:

  • To review the functions and molecular mechanisms of emerging synthetic lethal targets.
  • To discuss advancements in synthetic lethality theory and drug development.
  • To explore the integration of synthetic lethal drugs with conventional cancer treatments.

Main Methods:

  • Review of current literature on synthetic lethality, gene-gene interactions, and cancer therapeutics.
  • Analysis of emerging targets such as ATR, WEE1, and WRN.
  • Examination of clinical trial data and outcomes for synthetic lethal drugs.

Main Results:

  • Poly (ADP-ribose) polymerase (PARP) inhibitors are the first approved SL drugs.
  • Emerging targets like ATR, WEE1, and WRN show significant clinical potential.
  • Technological advances have improved the identification of SL targets and drug development.

Conclusions:

  • Synthetic lethality presents a promising avenue for personalized cancer treatment.
  • Combining SL drugs with traditional therapies may enhance clinical benefits.
  • Further research into SL mechanisms and drug combinations is crucial for future cancer therapy.
Keywords:
DNA repairPARP inhibitorscancer therapycombined strategysynthetic lethality

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