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Updated: Jun 5, 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 lethal strategies for the development of cancer therapeutics

Natalie Y L Ngoi1,2,3, David Gallo4, Carlos Torrado1

  • 1Department of Investigational Cancer Therapeutics (Phase I Clinical Trials Program), Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.

Nature Reviews. Clinical Oncology
|December 3, 2024
PubMed

Insights

Synthetic lethality uses two genetic alterations to impair cancer cell viability. This approach, enhanced by CRISPR-Cas9 screening, offers new therapeutic strategies and biomarkers for cancer treatment.

Area of Science:

  • Genetics
  • Cancer Biology
  • Drug Discovery

Background:

  • Synthetic lethality involves two genetic alterations that compromise cell viability.
  • Targeting synthetic lethal interactions presents therapeutic opportunities for cancers with undruggable pathways.
  • CRISPR-Cas9 technologies are pivotal in identifying novel synthetic lethal interactions.

Purpose of the Study:

  • To review established and emerging technologies for synthetic lethal drug discovery.
  • To discuss promising therapeutic strategies targeting synthetic lethal interactions.
  • To highlight the role of synthetic lethality in cancer therapy and biomarker development.

Main Methods:

  • High-throughput screening using CRISPR-Cas9.
  • Review of preclinical and clinical studies on synthetic lethality.
  • Analysis of therapeutic strategies targeting DNA damage response, epigenetic, metabolic, and proliferative pathways.

Main Results:

  • CRISPR-Cas9 screening is crucial for identifying synthetic lethal interactions.
  • Synthetic lethality offers potential for targeted cancer therapies and predictive biomarkers.
  • Clinical development is advancing for agents targeting DNA damage response pathways.

Conclusions:

  • Synthetic lethality is a promising avenue for developing novel cancer therapeutics.
  • Technological advancements are accelerating the discovery and development of synthetic lethal drugs.
  • Targeting synthetic lethal interactions across various pathways holds significant therapeutic potential.

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