Personalized Medicine—Guided Synthetic Lethality Targeting DNA Repair Pathways

Dear Colleagues,

Personalized medicine is an approach to the practice of medicine that uses information about a patient’s unique makeup and environment to customize the patient’s medical care to fit their individual requirements. For example, diagnostic testing is often employed for selecting appropriate and optimal therapies based on the context of a patient’s genetic, epigenetic, proteomic, and/or metabolomic content. In addition to specific treatment, personalized medicine can greatly aid the advancements of preventive care.

The phenomenon of synthetic lethality was first described in drosophila in the 1940s, and it was first proposed as an anticancer strategy in 1997. Two landmark papers in 2005 established a synthetic lethal interaction between BRCA1/2-mutations and poly(ADP)-ribose polymerase (PARP) inhibitors, which is driven by defects in homologous recombination (HR) in tumors with these mutations. Multiple PARP inhibitors are now FDA-approved for BRCA1/2-mutant cancers, which has established a proof-of-concept for personalized cancer therapy utilizing a synthetic lethal strategy targeting DNA repair.

In recent years, there has been tremendous progress in the identification of tumors from individual patients based on genetic, epigenetic, proteomic, and/or metabolomic content, for treatment using synthetic lethality-based approaches targeting various DNA repair pathways and proteins. Moreover, this approach has spurred the development of novel drugs which target specific DNA repair mechanisms.

This Special Issue will highlight current and emerging approaches to select individual tumors for treatment with DNA repair-inhibitor based treatment regimens using the concept of synthetic lethality.

Prof. Dr. Tomasz Skorski
Prof. Ranjit Bindra
Dr. Juan Vasquez
Guest Editors

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• DNA damage
• DNA repair
• personalized medicine
• synthetic lethality
• PARP inhibitor