About this Research Topic
Given that cancer cells almost always downregulate at least one DNA repair pathway, this opens up the possibility of using a synthetic lethality strategy to kill the cancer cells. This strategy was successfully demonstrated by the development of the PAPR inhibitors to kill BRCA-deficient cancer cells. Yet, more than 40% of cancer patients given PARP inhibitors frequently developed resistance because of restoring the defective DNA repair pathway and/or reactivating the alternative DNA repair pathways. To address this issue, novel cancer targets and structural insights for better precision medicine or combination therapy are required. For example, recent advances in cryo-EM have produced structural insights into several challenging protein complexes, such as NER complexes, revealing vital information on mechanism and therapeutic potential. Furthermore, we must think about how we may combine data from RNAi screening, CRISPR screening, and cancer genomic databases with known DDR and repair pathways to uncover better cancer targets with synthetic lethal interactions.
The goal of this research topic is to spark ideas and provide new findings and insights on the next breakthrough cancer targets for DNA damage response and repair inhibition. This topic collection invites all types of articles, such as perspectives, reviews, original research, and methods.
Areas to be covered in this research topic may include, but are not limited to:
• Structural, computational, and functional research of DDR and repair mechanisms
• Development of DDR and repair inhibitors
• Discovery of novel DDR and repair proteins, cancer targets, and biomarkers
• Advanced methods for screening synthetic lethal interactions and cancer genomic analysis in DDR
• (Pre)Clinical applications involving DDR and repair inhibitors.
Keywords: DDR, repair inhibition, cancer targets, repair proteins, cancer genomic analysis, synthetic lethality
Important Note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.