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Updated: Mar 13, 2026

A Data Integration Workflow to Identify Drug Combinations Targeting Synthetic Lethal Interactions
Published on: May 27, 2021
The transposable element-PARP axis underpins synthetic lethality and immunogenic vulnerability in blood cancer
Bernd B Zeisig1,2, Mohammad M Karimi1, Chi Wai Eric So1,2
1Comprehensive Cancer Centre, King's College London, London, United Kingdom.
Abstract:
Transposable elements (TEs) are emerging regulators of hematopoiesis and leukemia, creating vulnerabilities exploitable for therapy. Recent evidence shows that TE reactivation induces innate immune signaling, DNA damage responses, and dependence on poly(ADP-ribose) polymerase (PARP)-mediated protection, enabling synthetic lethality with PARP inhibition even in homologous recombination-proficient leukemias with epigenetic gene mutations. In this article, we highlight the biology underpinning this novel TE-PARP axis, its therapeutic implications, and strategies to expand PARP inhibition beyond HR-deficient cancers through rational combinations with immunotherapy and refined patient stratification.
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