Medizinische Universität Graz - Research portal
Selected Publication:
SHR Neuro Cancer Cardio Lipid Metab Microb
Fokas, E; Prevo, R; Hammond, EM; Brunner, TB; McKenna, WG; Muschel, RJ.
Targeting ATR in DNA damage response and cancer therapeutics.
Cancer Treat Rev. 2014; 40(1):109-17
Doi: 10.1016/j.ctrv.2013.03.002
Web of Science
PubMed
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- Co-authors Med Uni Graz
- Brunner Thomas Baptist
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- Abstract:
- The ataxia telangiectasia and Rad3-related (ATR) plays an important role in maintaining genome integrity during DNA replication through the phosphorylation and activation of Chk1 and regulation of the DNA damage response. Preclinical studies have shown that disruption of ATR pathway can exacerbate the levels of replication stress in oncogene-driven murine tumors to promote cell killing. Additionally, inhibition of ATR can sensitise tumor cells to radiation or chemotherapy. Accumulating evidence suggests that targeting ATR can selectively sensitize cancer cells but not normal cells to DNA damage. Furthermore, in hypoxic conditions, ATR blockade results in overloading replication stress and DNA damage response causing cell death. Despite the attractiveness of ATR inhibition in the treatment of cancer, specific ATR inhibitors have remained elusive. In the last two years however, selective ATR inhibitors suitable for in vitro and - most recently - in vivo studies have been identified. In this article, we will review the literature on ATR function, its role in DDR and the potential of ATR inhibition to enhance the efficacy of radiation and chemotherapy.
- Find related publications in this database (using NLM MeSH Indexing)
- Animals - administration & dosage
- Antineoplastic Agents - pharmacology, therapeutic use
- Ataxia Telangiectasia Mutated Proteins - antagonists & inhibitors, metabolism
- Checkpoint Kinase 1 - administration & dosage
- Clinical Trials as Topic - administration & dosage
- Combined Modality Therapy - administration & dosage
- DNA Damage - administration & dosage
- DNA Replication - administration & dosage
- Humans - administration & dosage
- Molecular Targeted Therapy - administration & dosage
- Neoplasms - drug therapy, enzymology
- Protein Kinase Inhibitors - pharmacology, therapeutic use
- Protein Kinases - metabolism
- Signal Transduction - administration & dosage
- Find related publications in this database (Keywords)
- ATR
- Cancer
- Replication stress
- DNA damage
- Radiation
- Chemotherapy
- Therapeutics