Resistance to DNA repair inhibitors in cancer.
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ICR Authors
Authors
Baxter, JS
Zatreanu, D
Pettitt, SJ
Lord, CJ
Zatreanu, D
Pettitt, SJ
Lord, CJ
Document Type
Journal Article
Date
2022-05-14
Date Accepted
2022-05-12
Abstract
The DNA damage response (DDR) represents a complex network of proteins which detect and repair DNA damage, thereby maintaining the integrity of the genome and preventing the transmission of mutations and rearranged chromosomes to daughter cells. Faults in the DDR are a known driver and hallmark of cancer. Furthermore, inhibition of DDR enzymes can be used to treat the disease. This is exemplified by PARP inhibitors (PARPi) used to treat cancers with defects in the homologous recombination DDR pathway. A series of novel DDR targets are now also under pre-clinical or clinical investigation, including inhibitors of ATR kinase, WRN helicase or the DNA polymerase/helicase Polθ (Pol-Theta). Drug resistance is a common phenomenon that impairs the overall effectiveness of cancer treatments and there is already some understanding of how resistance to PARPi occurs. Here, we discuss how an understanding of PARPi resistance could inform how resistance to new drugs targeting the DDR emerges. We also discuss potential strategies that could limit the impact of these therapy resistance mechanisms in cancer.
Citation
Molecular Oncology, 2022,
Source Title
Molecular Oncology
Publisher
WILEY
ISSN
1574-7891
eISSN
1878-0261
1878-0261
1878-0261
Collections
Research Team
Gene Function